Co-reporter:Hongcan Zhang, Wentao Wu, Xiaoqi Zhao, and Youliang Zhao
Macromolecules April 25, 2017 Volume 50(Issue 8) pp:3411-3411
Publication Date(Web):April 6, 2017
DOI:10.1021/acs.macromol.7b00220
Rational macromolecular design allows us to construct multiresponsive architectural polymers with a potential toward multipurpose applications. This study aims at synthesis and LCST-type thermoresponsive behaviors of multisensitive linear and cyclic graft copolymers with polyacrylamide backbone and hydrophilic PEG grafts. The cloud point could be tuned by many factors, and the effect of cyclization was confirmed by the elevated cloud point in H2O up to 12.8 °C under same conditions. The PEG-connecting Y junctions with dual amide, thioether, and tertiary amine groups allowed thermo-, solvent-, pH-, and CO2-switchable inter/intramolecular hydrogen bonding interactions and hence resulted in unusual solvent (H2O or D2O) and pH (about 6.8–8.5) dependent phase transition and irreversible CO2-responsive behavior. Meanwhile, the solution blending could lead to one or two phase transition(s) dependent on types and compositions of the blends. The meticulous introduction of multifunctional Y junctions into graft copolymers offers a versatile route to adjust multitunable thermoresponsive properties.
Co-reporter:Hongcan Zhang;Jian Zhang;Wenxue Dai
Polymer Chemistry (2010-Present) 2017 vol. 8(Issue 37) pp:5749-5760
Publication Date(Web):2017/09/26
DOI:10.1039/C7PY01351E
The simple and straightforward construction of multi-responsive systems with tunable LCST and UCST dual phase transitions is a great challenge. This study affords an efficient route to tune cloud points via control over the chemical composition of hydroxyl and diethylamino bearing poly(amido thioether)s which were prepared by one-pot thiol–amine–acrylate polyaddition. Owing to the balance of inter/intrachain interactions, various copolymers could exhibit LCST (fOH < 0.84), LCST–UCST (fOH = 0.84–0.89) and UCST (fOH > 0.89) behaviors relying on the hydroxyl fraction in comonomer units. Meanwhile, the thermoresponsive behaviors of copolymer solutions could be efficiently tuned via switching the solvent and solution pH, applying CO2/N2 bubbling, and oxidation. The success of this study further paves the way for the robust synthesis and practical applications of smart polymers with double thermoresponsivity.
Co-reporter:Hui He;Shuangshuang Ji;Yang He;Aijun Zhu;Yelin Zou;Yibin Deng;Hengte Ke;Hong Yang;Zhengqing Guo;Huabing Chen
Advanced Materials 2017 Volume 29(Issue 19) pp:
Publication Date(Web):2017/05/01
DOI:10.1002/adma.201606690
Photoconversion tunability of fluorophore dye is of great interest in cancer nanomedicine such as fluorescence imaging, photodynamic therapy (PDT), and photothermal therapy (PTT). Herein, this paper reports wavelength-dependent photoconversional polymeric vesicles of boron dipyrromethene (Bodipy) fluorophore for either PDT under 660 nm irradiation or PTT under 785 nm irradiation. After being assembled within polymeric vesicles at a high drug loading, Bodipy molecules aggregate in the conformations of both J-type and H-type, thereby causing red-shifted absorption into near-infrared region, ultralow radiative transition, and ideal resistance to photobleaching. Such vesicles further possess enhanced blood circulation, preferable tumor accumulation, as well as superior cell uptake as compared to free Bodipy. In particular, the vesicles mainly generate abundant intracellular singlet oxygen for PDT treatment under 660 nm irradiation, while they primarily produce a potent hyperthermia for PTT with tumor ablation through singlet oxygen-synergized photothermal necrosis under 785 nm irradiation. This approach provides a facile and general strategy to tune photoconversion characteristics of fluorophore dyes for wavelength-dependent photoinduced cancer therapy.
Co-reporter:Huanhuan Liu;Jian Zhang;Wenxue Dai
Polymer Chemistry (2010-Present) 2017 vol. 8(Issue 44) pp:6865-6878
Publication Date(Web):2017/11/14
DOI:10.1039/C7PY01638G
ABCD star quaterpolymers acquired by precision synthesis may provide us with insights into self-assembly due to their fused architectures of different arm segments and a central core. Considering the crucial role of external stimuli in smart materials, the aims of this study are the facile synthesis of a pH/redox-responsive 4-arm miktoarm star and the study of its stimuli-dependent aggregation behaviors. A click reaction between azide/bromine-functionalized poly(ethylene glycol)-block-polystyrene (PEG-b-PSt) and alkyne/disulfide-functionalized poly(ε-caprolactone)-block-poly(tert-butyl acrylate) (PCL-b-PtBA) and subsequent selective hydrolysis were used to synthesize the target star with bromomethyl and disulfide functionalities in the core and a poly(acrylic acid) (PAA) segment. The PEG-PSt-PCL-PAA star can self-assemble into nanocapsules with hollow caves; the sizes and morphologies of these assemblies are dependent on pH and reductive stimuli due to stimuli-tunable destabilization and reassembly. By virtue of polyion and hydrogen bonding complexation using a partly quaternized copolymer, the nanocapsules can be further converted into versatile coaggregates such as compound vesicles and micelles, multicompartment vesicles, and hyperbranched micelles. Our research affords a robust method to synthesize core-functionalized stimuli-labile multicomponent miktoarm stars; these stimuli-responsive nanocapsules hold great promise in smart biomedical and interfacial materials.
Co-reporter:Weidong Pan, Huanhuan Liu, Hongcan Zhang and Youliang Zhao
Polymer Chemistry 2016 vol. 7(Issue 16) pp:2870-2881
Publication Date(Web):05 Apr 2016
DOI:10.1039/C6PY00267F
Synthesis of multicomponent miktoarm stars (MMS) has attracted much attention due to their intriguing morphologies and multipurpose applications. Thus far, the examples of stimuli-cleavable MMS are very scarce. This study aims at modular synthesis of the first example of an acid-labile ABCD star quaterpolymer and exploring its potential in smart drug delivery systems. An alkyne-core-functionalized ABC star terpolymer was initially synthesized via the “core-first” method, and then CuAAC was performed to achieve the desired star with poly(N-isopropylacrylamide) (PNIPAM, A), poly(2-diisopropylaminoethyl methacrylate) (PDPA, B), poly(ε-caprolactone) (PCL, C), and acetal-linked poly(ethylene glycol) (aPEG, D) segments. Upon an acid stimulus, the ABCD star was liable to “degrade” into a mixture of PEG and AB′C star with a protonated PDPA (B′) segment, and the differences in the topology and composition further induced time-dependent morphological transformations of copolymer aggregates. With prolonging time, various morphologies involving large compound micelles (0 h), flower-like micelles (1 h), small micelles and their aggregates (3 h), and compound micelles with a reduced size (t ≥ 12 h) were observed from TEM images. Doxorubicin-loaded copolymer aggregates exhibited accelerated drug release kinetics upon thermo and pH stimuli, and the micellar system may hold great promise for biomedical applications due to its relatively low cytotoxicity and stimuli-tunable release properties. In addition to developing a modular “3 + 1” approach to generate star quaterpolymers, this study underlies systematic research studies on properties and applications of functional MMS and their derivatives.
Co-reporter:Min Tong, Xiaonan An, Weidong Pan, Huanhuan Liu and Youliang Zhao
Polymer Chemistry 2016 vol. 7(Issue 12) pp:2209-2221
Publication Date(Web):26 Feb 2016
DOI:10.1039/C6PY00182C
This study aims at synthesis and properties of multifunctional AB2mC2m-type toothbrush-like copolymers. The target copolymers comprising a relatively long linear PNIPAM block and a relatively short comb-like block with V-shaped (PAA)2 and (PCL)2 grafts were controllably synthesized by multistep reactions. DSC results revealed that various segments in copolymers were partly compatible. The high grafting density, structural diversity and/or crystalline nature of PCL segments allowed stimuli-induced versatile morphological transitions, and the terpolymer was liable to self-assemble into spherical micelles (25 °C), sea cucumber-like micelles (25 °C, pH 5.3), vesicles (37 °C), and spherical micelles and their aggregates (37 °C, pH 5.3) due to the change in inter- and intramolecular interactions. As compared with the copolymer aggregates formed from the linear analogue with a similar composition, toothbrush-like copolymer based aggregates were liable to exhibit reduced critical aggregation concentration, higher drug loading efficiency, faster release kinetics and enhanced storage stability, and they could act as more efficient vehicles for thermo, pH and additive (β-CD and GSH) triggered drug delivery. Upon a single stimulus or combined stimuli, doxorubicin-loaded aggregates exhibited significantly accelerated drug release kinetics. Our study affords a robust method to generate novel heterografted toothbrush-like copolymers, and the success of this research has important implications for exploring the unique properties and bioapplications of nonlinear multicomponent copolymers.
Co-reporter:Huanhuan Liu, Weidong Pan, Min Tong and Youliang Zhao
Polymer Chemistry 2016 vol. 7(Issue 8) pp:1603-1611
Publication Date(Web):26 Jan 2016
DOI:10.1039/C5PY01960E
The exploration on robust methods to construct star copolymers has attracted much attention. Owing to the great challenge in synthesis, the examples of miktoarm stars with chemical compositions up to five or more are very scarce. This study aims at developing a modular and orthogonal approach to synthesize multicomponent stars via a one-pot strategy using distinct building blocks. Tandem CuAAC and Diels–Alder reactions were utilized to generate an ABCDE star comprising poly(ε-caprolactone) (PCL, A), poly(tert-butyl acrylate) (PtBA, B), poly(L-lactide) (PLLA, C), poly(N-isopropylacrylamide) (PNIPAM, D) and poly(5-methyl-5-allyloxycarbonyl-1,3-dioxane-2-one) (PMAC, E) arms, and a subsequent hydrolysis afforded an AB′CDE (B′ = poly(acrylic acid)) star with clickable and dual-sensitive segments. The star copolymers were liable to self-assemble into intriguing morphologies involving vesicles, spherical micelles and large compound micelles which could be tuned by adopting thermal and pH stimuli. The modular synthesis using orthogonal chemistry allows us to prepare ABCDE-type stars with well-controlled molecular weight, tunable composition, and versatile functions. The success of this study further paves the way for facile synthesis of multifunctional star quintopolymers and their derivatives with multipurpose applications.
Co-reporter:Xiaonan An;Qingquan Tang;Wen Zhu;Ke Zhang
Macromolecular Rapid Communications 2016 Volume 37( Issue 12) pp:980-986
Publication Date(Web):
DOI:10.1002/marc.201600152
Co-reporter:Xiaonan An, Aijun Zhu, Huanhuan Luo, Hengte Ke, Huabing Chen, and Youliang Zhao
ACS Nano 2016 Volume 10(Issue 6) pp:5947
Publication Date(Web):June 10, 2016
DOI:10.1021/acsnano.6b01296
Stimuli-responsive nanoparticles with target capacity are of great interest in drug delivery for cancer therapy. However, the challenge is to achieve highly smart release with precise spatiotemporal control for cancer therapy. Herein, we report the preparation and properties of multi-stimuli-responsive nanoparticles through the co-assembly of a 3-arm star quaterpolymer with a near-infrared (NIR) photothermal agent and chemotherapeutic compound. The nanoparticles can exhibit NIR light/pH/reduction–responsive drug release and intracellular drug translocation in cancer cells, which further integrate photoinduced hyperthermia for synergistic anticancer efficiency, thereby leading to tumor ablation without tumor regrowth. Thus, this rational design of nanoparticles with multiple responsiveness represents a versatile strategy to provide smart drug delivery paradigms for cancer therapy.Keywords: cancer therapy; miktoarm star copolymer; multisensitive nanoparticles; stimuli-triggered release; synergistic effect
Co-reporter:Huanhuan Liu, Cangxia Li, Dandan Tang, Xiaonan An, Yanfei Guo and Youliang Zhao
Journal of Materials Chemistry A 2015 vol. 3(Issue 19) pp:3959-3971
Publication Date(Web):17 Apr 2015
DOI:10.1039/C5TB00473J
Thermo-, pH and reduction triggered drug delivery vehicles based on dual-cleavable polymeric micelles were investigated. A comblike copolymer (G3) comprising one disulfide linkage and PEG, PCL and acetal-bridged PCL-b-PNIPAM grafts was controllably synthesized by successive RAFT copolymerization, ring-opening polymerization and adductive reaction. G3 was liable to self-assemble into spherical micelles at 25 °C and toroidal micelles at 37 °C, and the aggregates formed at 37 °C could be further converted into multicompartment micelles (pH 5.3), spherical micelles (DTT) and hyperbranched or necklace-like cylinders (pH 5.3 + DTT) upon external stimuli due to the stimuli-triggered topological transformation and reaggregation of copolymer aggregates. Upon external stimuli, doxorubicin (DOX) loaded G3 and G3/β-CD (co)aggregates could exhibit accelerated drug release kinetics. The apparent release rates varied in the range 0.072–0.403 h−1 (for G3 aggregates) and 0.142–0.458 h−1 (for G3/β-CD coaggregates), revealing that the drug release system bearing host–guest interactions could further extend the ranges of the release rate and cumulative release. Although β-CD and G3 micelles lacked notable cytotoxicity, the cytotoxicity of DOX-loaded (co)aggregates to 4T1 cells was higher than free DOX. CLSM images revealed that DOX-loaded copolymer aggregates may enter cells via endocytosis in a manner of nanocomplexes. Our study can not only extend the potential of stimuli-cleavable copolymers toward biomedical applications but also enrich the family of multi-responsive copolymer aggregates.
Co-reporter:Bin Mo, Huanhuan Liu, Xiangdong Zhou and Youliang Zhao
Polymer Chemistry 2015 vol. 6(Issue 18) pp:3489-3501
Publication Date(Web):01 Apr 2015
DOI:10.1039/C5PY00132C
Different from hyperbranched star-like polymers and dendritic brushes, dendritic-unit-bridged hyperbranched graft copolymers (DHGCs) with branching point linked branches and linear grafts can be regarded as a new subclass of hyperbranched-graft-linear copolymers. This study aims at the synthesis and properties of photocleavable DHGCs comprising oligomeric branches composed of poly(ethylene glycol) methyl ether acrylate (PEGA) units, linear poly(ε-caprolactone) (PCL) grafts and o-nitrobenzyl ester (ONBE) moieties in the dendritic unit. Based on a multifunctional inimer 3-((2-acryloyloxymethyl-2-hydroxymethyl)propionyloxy)methyl-2-nitrobenzyl 4-cyano-4-(phenylcarbonothioylthio)pentanoate (ANCP), functional DHGCs were controllably synthesized via two step reactions. RAFT copolymerization afforded hyperbranched poly(ANCP-co-PEGA) (PAP), followed by CL polymerization to achieve PAP-g-PCL. Upon photo-cleavage, hyperbranched PAP was converted into linear polymers, and PAP-g-PCL was readily degraded into mixtures of linear, star and graft polymers. With increasing UV irradiation time, the PAP-g-PCL micelles were gradually evolved into vesicles and multicompartment vesicles due to photo-triggered cleavage and reaggregation. Upon normal and on-demand UV irradiation, the release kinetics for controlled release of Nile red from copolymer aggregates could be tuned in a wide range, revealing the great potential in smart drug delivery systems. This study affords a versatile method to construct photolabile DHGCs, which opens up a new route to explore unique properties of novel topological copolymers.
Co-reporter:Cangxia Li, Huanhuan Liu, Dandan Tang and Youliang Zhao
Polymer Chemistry 2015 vol. 6(Issue 9) pp:1474-1486
Publication Date(Web):15 Dec 2014
DOI:10.1039/C4PY01495B
Novel amphiphilic (PEG)m(PCL)n (m ≈ n ≈ 23) miktoarm stars with a disulfide-linked epoxy-functionalized branched core were controllably synthesized via three step reactions comprising self-condensing vinyl polymerization via reversible addition–fragmentation chain transfer, epoxy-carboxyl coupling reaction and ring-opening polymerization. The star copolymers were characterized by 1H NMR spectra, GPC-MALLS, DSC and reduction-triggered degradation. Postpolymerization modification via epoxy-carboxyl/phenol coupling reactions allowed attaching dual-reactive functionalities including coumarin, alkyne and alkyl bromide onto the branched core. In water and THF–water mixtures, a coumarin-modified star copolymer could aggregate into some intriguing morphologies including hyperbranched micelles and large vesicles due to the influence of solvent polarity on aggregation behaviors. Owing to the differences in the isolation of fluorophores from solvents and restricted molecular motion, coumarin-functionalized stars exhibited adjustable fluorescence properties in water and THF–water mixtures, and their aqueous solution had a maximum quantum yield (ΦF = 44.2%). The solutions of star copolymers and their reduction-cleaved copolymers were of different hydrodynamic diameters, and the ΦF(star)/ΦF(cleaved copolymer) values were 1.85 (in THF), 3.00 (in water) and ranged between 1.29 and 2.58 in THF–water mixtures, revealing that the aggregation behaviors and fluorescence properties were strongly dependent on polymeric architecture, location of fluorophores and solvent polarity. Our study affords a versatile method to construct functional miktoarm stars with a multi-reactive branched core, and coumarin-functionalized star copolymers may have a great potential as solvent polarity and reduction dual-sensitive imaging materials in “green” ink, coatings and nanocarriers for biomedical applications.
Co-reporter:Yanfei Guo, Huanhuan Liu, Dandan Tang, Cangxia Li and Youliang Zhao
Polymer Chemistry 2015 vol. 6(Issue 14) pp:2647-2658
Publication Date(Web):16 Feb 2015
DOI:10.1039/C4PY01741B
Facile construction of solid substrates grafted with quaternized copolymers by two step reactions comprising the alkoxysilane–hydroxyl coupling reaction, quaternization and RAFT polymerization is described. Silica nanoparticles grafted with poly(N,N-dimethylaminoethyl methacrylate) (PDMA) were initially prepared via tandem linking reaction and RAFT polymerization and acted as a versatile platform to generate three types of ion-bearing topological copolymers grafted silica. Bromide-functionalized agents and polymers were grafted onto the surface-tethered PDMA backbone to form quaternized random and comblike copolymers grafted silica, and concurrent quaternization and RAFT processes were performed to generate silica nanoparticles grafted with toothbrushlike copolymers comprising poly(methyl methacrylate), polystyrene, poly(N-isopropylacrylamide) and poly(tert-butyl acrylate) segments. Free polymers and grafted side chains obtained by a tandem approach usually have similar chain length and low polydispersity, as evident from hydrolysis, GPC and 1H NMR analyses. The quaternization efficiency of graft reactions was in the range of 34–79% (for attaching small molecules) and 3.8–7.4% (for grafting polymeric chains). Our preliminary results revealed that the surface wettability of hybrid films was dependent on some factors such as macromolecular architecture, quaternization degree, chemical composition and temperature. This study affords a straightforward and versatile method to construct quaternized macromolecular architectures grafted onto hydroxyl-rich solid substrates, and the resulting silica–polymer hybrids may have a great potential in stimuli-responsive emulsifiers, surface and antibacterial materials.
Co-reporter:Wen Zhu;Zi Li;Ke Zhang
Macromolecular Rapid Communications 2015 Volume 36( Issue 22) pp:1987-1993
Publication Date(Web):
DOI:10.1002/marc.201500367
Co-reporter:Huanhuan Liu, Xiao Jiang, Rongjian Bian, Min Tong, Dandan Tang, Xiangdong Zhou, Youliang Zhao
Polymer 2015 Volume 64() pp:249-259
Publication Date(Web):1 May 2015
DOI:10.1016/j.polymer.2015.01.059
•Styrenic and maleimidic inimers were used to generate novel A2mB2n stars.•They had controlled molecular weight and composition and precise microstructure.•The high bromide functionality was confirmed by chain extension polymerization.•Star copolymers had uniform arm length, evident from cleavage of arms.•This study paves way for rapid synthesis of miktoarm stars and their derivatives.Controlled synthesis of A2mB2n-type (m ≈ n ≈ 8) starlike copolymers comprising an oligomeric poly(styrene-co-maleimide) core and two types of V-shaped arms individually generated by ATRP and ROP was described. Multistep syntheses involving RAFT copolymerization, end group removal, ATRP of vinyl monomers such as styrene (St), methoxyethyl methacrylate (MEMA) and tert-butyl acrylate (tBA), and ROP of ε-caprolactone (CL) were used to construct the target miktoarm stars with controlled molecular weight and relatively low polydispersity (PDI = 1.07–1.22). The resultant star copolymers had high bromide functionality and uniform chain length of ATRP-generated arms, evident from chain extension polymerization and cleavage of arms. Meanwhile, a pH-responsive (PAA)2m(PCL)2n star was also obtained by selective hydrolysis. The synthetic strategy via combination of RAFT copolymerization and “core first” approach is versatile in constructing various A2mB2n stars, and this study further paves way for facile synthesis and properties of new types of miktoarm stars.
Co-reporter:Aijun Zhu, Ke Miao, Yibin Deng, Hengte Ke, Hui He, Tao Yang, Miao Guo, Yanli Li, Zhengqing Guo, Yangyun Wang, Xiangliang Yang, Youliang Zhao, and Huabing Chen
ACS Nano 2015 Volume 9(Issue 8) pp:7874
Publication Date(Web):July 16, 2015
DOI:10.1021/acsnano.5b02843
Smart nanocarriers are of particular interest as nanoscale vehicles of imaging and therapeutic agents in the field of theranostics. Herein, we report dually pH/reduction-responsive terpolymeric vesicles with monodispersive size distribution, which are constructed by assembling acetal- and disulfide-functionalized star terpolymer with near-infrared cyanine dye and anticancer drug. The vesicular nanostructure exhibits multiple theranostic features including on-demand drug releases responding to pH/reduction stimuli, enhanced photothermal conversion efficiency of cyanine dye, and efficient drug translocation from lysosomes to cytoplasma, as well as preferable cellular uptakes and biodistribution. These multiple theranostic features result in ultrahigh-contrast fluorescence imaging and thermo-chemotherapy-synergized tumor ablation. The dually stimuli-responsive vesicles represent a versatile theranostic approach for enhanced cancer imaging and therapy.Keywords: cancer imaging; photothermal therapy; stimuli-responsive release; synergistic effect; vesicles;
Co-reporter:Huanhuan Liu;Dandan Tang;Rupei Tang
Science China Chemistry 2015 Volume 58( Issue 11) pp:1724-1733
Publication Date(Web):2015 November
DOI:10.1007/s11426-015-5436-4
This study aims at versatile synthesis of 3-arm ABC-type (A=poly(ε-caprolactone), PCL; B=poly(N-isopropylacrylamide), PNIPAM; C=poly(tert-butyl acrylate), PtBA, or poly(acrylic acid), PAA) miktoarm star copolymers with a reducible disulfide linkage. Using 2-((2-((2-hydroxymethyl-2-((2-bromo-2-methyl)propionyloxy)methyl)propionyloxy)ethyl)disulfanyl)ethyl 4-cyano-4-(phenylcarbonothioylthio)pentanoate (HBCP) as a heterotrifunctional initiator, consecutive ring-opening polymerization (ROP) of ε-caprolactone (CL), reversible addition-fragmentation chain transfer (RAFT) polymerization of N-isopropylacrylamide (NIPAM) and atom transfer radical polymerization (ATRP) of tert-butyl acrylate (tBA) afforded ABC1 star, and followed by a subsequent hydrolysis to give ABC2 star. 1H nuclear magnetic resonance (1H NMR) and gel permeation chromatography (GPC) analyses revealed the desired stars and their precursors had well-controlled molecular weight and relatively low polydispersity (PDI⩽1.12). As confirmed by GPC analysis, the disulfide linkage in ABC1 star could be efficiently cleaved upon reductive stimulus, during which the topology was converted from star terpolymer to mixtures of homopolymer (B) and diblock copolymer (AC1). In addition to acting as nanocarriers for stimuli-triggered drug delivery systems, ABC stars with terminal bromide, dithiobenzoate and hydroxyl functionalities are expected to form other reduction-cleavable multicomponent copolymers such as (BC-graft-A)m and dendritic graft copolymers via postpolymerization modification. Our research affords a straightforward “core-first” method to construct multifunctional star terpolymers with stimuli-responsive arms and reduction-labile linkage.
Co-reporter:Ke Miao, Wei Shao, Huanhuan Liu and Youliang Zhao
Polymer Chemistry 2014 vol. 5(Issue 4) pp:1191-1201
Publication Date(Web):08 Nov 2013
DOI:10.1039/C3PY01049J
A novel disulfide- and acetal-linked graft copolymer (SACG) comprising acetal-bridged poly(ε-caprolactone)-b-poly(ethylene glycol) and PEG pendent chains and relatively short polymethacrylate backbone (DP ≈ 24) was synthesized and self-assembled for in vitro encapsulation and release of an anticancer drug, doxorubicin (DOX). Three-step reactions involving (i) RAFT copolymerization of 2-hydroxyethyl methacrylate and poly(ethylene glycol) methyl ether methacrylate, (ii) ring-opening polymerization to generate PCL chains, and (iii) hydroxyl-vinyloxy adductive reaction to introduce acid-cleavable PEG segments were used to achieve the target copolymer. Meanwhile, well-defined normal (CP) and disulfide-linked (SCP) poly(PEG-co-PCL) comb-like copolymers and acid-cleavable poly(PEG-co-PCL)-graft-MVPEG copolymer (ACG) were synthesized and acted as analogues of SACG upon external stimuli. The macromolecular architecture significantly affected the melting and crystallization behaviors and aggregation properties of copolymers, and the difference in topology and location of cleavable linkages resulted in distinctly different stimuli-triggered drug release behaviors. Owing to the dissociation and reaggregation of cleaved copolymer aggregates, stimuli-cleavable aggregates in response to external stimuli (pH 5.0, 10 mM DTT) could exhibit faster release kinetics than CP aggregates, and the maximum increment of cumulative release from various aggregates for 72 h was liable to decrease in the order SACG > ACG > SCP > CP. The cumulative release from SACG aggregates could be adjusted in the widest range via addition of different stimuli, revealing the great potential of dually cleavable copolymer aggregates in smart drug delivery systems.
Co-reporter:Huanhuan Liu, Ke Miao, Guangdong Zhao, Cangxia Li and Youliang Zhao
Polymer Chemistry 2014 vol. 5(Issue 8) pp:3071-3080
Publication Date(Web):05 Mar 2014
DOI:10.1039/C3PY01601C
The synthesis and properties of a star quintopolymer comprising poly(ethylene glycol) (PEG, A), poly(ε-caprolactone) (PCL, B), polystyrene (PSt, C), poly(L-lactide) (PLLA, D), and poly(acrylic acid) (PAA, E) segments were described. Terminal diazide functionalized PEG (PEG-(N3)2), alkyne-mid-functionalized PCL-b-PSt and PLLA-b-PtBA diblock copolymers acted as building blocks to synthesize the target ABCDE star via modular synthesis. DSC analyses revealed that star copolymers usually exhibited complex chain relaxation and melting behaviors although arm segments were partly compatible. Various copolymers could self-assemble into vesicles (for ABC and ABCDE stars) and micelles (for the DE copolymer) in aqueous solution, and the release rate of doxorubicin from various aggregates at pH 7.4 decreased in the order DE > ABCDE star > ABC star. For the same types of aggregates, the increment in the cumulative amount at pH 5.3 for 72 h was 66.9% (for ABCDE vesicles) and 92.5% (for DE micelles), higher than that at pH 7.4 in the same period, revealing the remarkably accelerated release kinetics under acidic conditions. The ABCDE vesicles had great potential as controlled delivery vehicles due to their excellent stability, satisfactory drug loading efficiency, and pH-responsive drug release properties.
Co-reporter:Dandan Tang, Xiao Jiang, Huanhuan Liu, Cangxia Li and Youliang Zhao
Polymer Chemistry 2014 vol. 5(Issue 16) pp:4679-4692
Publication Date(Web):27 May 2014
DOI:10.1039/C4PY00332B
The synthesis and properties of novel (A-g-D)(B-alt-C)mD-type heterografted toothbrush-like copolymers are described. The target copolymers comprised three types of building blocks, involving a terminal comb-like block with a quaternization bridging poly(N,N-dimethylaminoethyl methacrylate) (PDMA, A) substrate and D grafts, a middle comb-like block with a poly(styrene-alt-maleimide) backbone and alternating PEG (B) and PCL (C) grafts, and a terminal D segment involving poly(N-isopropylacrylamide) (PNIPAM), poly(methyl methacrylate) (PMMA), polystyrene (PSt) and poly(methyl acrylate) (PMA). The combination of quaternization and RAFT processes allowed for the controlled synthesis of the target copolymers with a precise microstructure and tunable composition and grafting density. With the changes in macromolecular architecture, chemical composition and grafting density, toothbrush-like copolymers were liable to exhibit different physicochemical properties such as chain relaxation, melting, crystallization and self-assembly behavior. The introduction of chemical heterogeneity into non-responsive toothbrush-like copolymers could endow polymer films with notable thermo-dependent wettability due to accelerated surface penetration and reconstruction. Meanwhile, the drug release properties of PNIPAM-based aggregates were significantly affected by temperature, additives and end groups, revealing their potential as promising controlled delivery vehicles. In addition to developing a general approach towards the construction of sequence-defined toothbrush-like copolymers with multicomponent grafts and variable grafting densities, our study further extended their potential applications in stimuli-sensitive surfaces and biomedical materials via changing the compatibility and supramolecular interactions.
Co-reporter:Ke Miao, Huanhuan Liu and Youliang Zhao
Polymer Chemistry 2014 vol. 5(Issue 10) pp:3335-3345
Publication Date(Web):06 Mar 2014
DOI:10.1039/C3PY01767B
Novel 5-arm PEG(PCL)2(PNIPAM)2 (S1) and PEG(PCL)2(PAA)2 (S3) star terpolymers were synthesized, and their aggregates formed by a single star or mixed stars were efficiently used for loading and release of doxorubicin upon dual and triple stimuli. The star terpolymers had two disulfide moieties and poly(ethylene glycol) (PEG, A), poly(ε-caprolactone) (PCL, B), poly(N-isopropylacrylamide) (PNIPAM, C1), poly(tert-butyl acrylate) (PtBA, C2), and poly(acrylic acid) (PAA, C3) segments. Terminal diazide functionalized PEG (PEG-(N3)2) and alkyne-mid-functionalized PCL-b-PNIPAM and PCL-b-PtBA diblock copolymers were subjected to an azide–alkyne cycloaddition reaction to generate AB2C2 (C = C1 and C2) stars followed by selective hydrolysis to obtain a PEG(PCL)2(PAA)2 star. Polymeric micelles were prepared by self-assembly of a single star in aqueous solution, and coaggregates were obtained by coassembly of S1 and S3 mixtures. Various polymeric aggregates had great potential as controlled delivery vehicles due to their reasonable drug loading efficiency and stimuli-adjustable drug release properties. As compared with dually sensitive micelles formed from a single star, triply stimuli-responsive coaggregates may be more promising as controlled delivery vehicles since the drug release properties can be potentially adjusted by various external stimuli and composition of star mixtures.
Co-reporter:Xiao Jiang, Wei Shao, Kun Jiang, Meijing Zhang, Huanhuan Liu, Chunnuan Ye and Youliang Zhao
Polymer Chemistry 2013 vol. 4(Issue 11) pp:3272-3281
Publication Date(Web):05 Apr 2013
DOI:10.1039/C3PY00217A
The synthesis and postfunctionalization of A(BC)mD (A = PDMA; B = PEG; C = PCL; D = PNIPAM, PtBA and PMA) comblike block copolymers comprising alkyne and tertiary amino functionalities and alternating PEG and PCL grafts are described. Three-step successive RAFT processes using prop-2-ynyl 4-(benzodithioyl)-4-cyanopentanoate as an original mediator were used to synthesize amphiphilic PDMA(PEG-alt-PCL)mPM (m ≈ 7) heterografted copolymers, in which the PEG and PCL segments were introduced by the alternating copolymerization of styrenic and maleimidic macromonomers. GPC-MALLS and 1H NMR results indicated that the resultant quaterpolymers were of well-controlled molecular weight and relatively low polydispersity (PDI = 1.12–1.25). The combination of end group transformation and the azide–alkyne “click” reaction afforded (A(BC)mD)n (n ≈ 4) comblike-linear multiblock copolymer and (A(BC)mD)x (x ≈ 7) dendritic graft copolymer, and Menschutkin reaction between A(BC)mD copolymer and bromide-functionalized small molecule/macromolecule gave an ion-bearing A′(BC)mD comblike block copolymer and A(BC)mD-graft-E toothbrushlike copolymer, revealing the great potential of postpolymerization modification in novel architecture construction. Preliminary results indicated that the introduction of various functionalities and polymer segments into brushlike copolymers via the quaternization process could affect the chain relaxation and melting behaviors, solubility, and surface wettability of polymer films.
Co-reporter:Wei Shao, Ke Miao, Huanhuan Liu, Chunnuan Ye, Jianzhong Du and Youliang Zhao
Polymer Chemistry 2013 vol. 4(Issue 11) pp:3398-3410
Publication Date(Web):17 Apr 2013
DOI:10.1039/C3PY00252G
Disulfide- and acetal-functionalized comb-like copolymers (SACP) with poly(ε-caprolactone) (PCL) and poly(ethylene glycol) (PEG) side chains and a polymethacrylate backbone were synthesized and self-assembled for in vitro encapsulation and release of an anticancer drug, doxorubicin (DOX). Three step reactions including RAFT copolymerization of 2-hydroxyethyl methacrylate and poly(ethylene glycol) methyl ether methacrylate mediated by a disulfide-functionalized RAFT agent, hydroxyl-vinyloxy addition reaction to introduce acid cleavable PEG segments, and CL polymerization to grow PCL chains were used to generate the target dual-sensitive comb-like copolymers. Meanwhile, well-defined normal comb-like polymers (CP), acid-cleavable comb-like polymers (ACP) and disulfide-linked comb-like polymers (SCP) with PEG and PCL pendent chains were also prepared and acted as analogues of SACP. All the resultant comb-like copolymers had the desired chemical structures, well-controlled molecular weight and relatively low polydispersity (PDI = 1.09–1.16), evident from 1H NMR and GPC-MALLS analyses. DLS and TEM measurements revealed that these copolymers were liable to self-assemble into micelles or large compound micelles in aqueous solution, and SACP aggregates could be dissociated and reaggregated in the presence of acidic PBS solution (pH 5.0) or 10 mM DL-dithiothreitol (DTT). Compared with CP aggregates with a lack of cleavable linkage, ACP, SCP and SACP aggregates upon acid and reduction stimuli could quickly release the encapsulated DOX, and the cumulative release from SACP aggregates could be roughly adjusted by addition of a single stimulus or dual stimuli. These results confirmed their great potential as novel nanocarriers and delivery systems.
Co-reporter:Meijing Zhang, Huanhuan Liu, Wei Shao, Ke Miao, and Youliang Zhao
Macromolecules 2013 Volume 46(Issue 4) pp:1325-1336
Publication Date(Web):February 11, 2013
DOI:10.1021/ma3025283
Facile construction of novel functional dendritic copolymers by combination of self-condensing vinyl polymerization, sequence-controlled copolymerization and RAFT process was presented. RAFT copolymerization of a disulfide-linked polymerizable RAFT agent and equimolar feed ratio of styrenic and maleimidic macromonomers afforded multicleavable AmBn dendritic comblike copolymers with alternating PEG (A) and PCL (B) grafts, and a subsequent chain extension polymerization of styrene, tert-butyl acrylate, methyl methacrylate, and N-isopropylacrylamide gave AmBnCo dendritic toothbrushlike copolymers. (PEG)m(PCL)n copolymers obtained were of adjustable molecular weight, relatively low polydispersity (PDI = 1.10–1.32), variable CTA functionality (fCTA = 4.3–7.5), and similar segment numbers of PEG and PCL grafts, evident from 1H NMR and GPC-MALLS analyses. Their branched architecture was confirmed by (a) reduction-triggered degradation, (b) decreased intrinsic viscosities and Mark–Houwink–Sakurada exponent than their “linear” analogue, and (c) lowered glass transition and melting temperatures and broadened melting range as compared with normal AmBn comblike copolymer. In vitro drug release results revealed that the drug release kinetics of the disulfide-linked AmBn copolymer aggregates was significantly affected by macromolecular architecture, end group and reductive stimulus. These stimuli-responsive and biodegradable dendritic copolymer aggregates had a great potential as controlled delivery vehicles.
Co-reporter:Xiao Jiang, Meijing Zhang, Shixian Li, Wei Shao and Youliang Zhao
Chemical Communications 2012 vol. 48(Issue 79) pp:9906-9908
Publication Date(Web):13 Aug 2012
DOI:10.1039/C2CC35275C
A straightforward strategy involving a RAFT process and ring-opening polymerization was used to construct symmetric reduction-responsive amphiphilic A2mB2nC2 (m ≈ n ≈ 3) starlike terpolymers with precise microstructure, which could be efficiently converted into thiol-functionalized telechelic stars, degraded AmBnC miktoarm stars and comblike-linear multiblock copolymers via postmodification.
Co-reporter:Guangdong Zhao, Peipei Zhang, Chengbo Zhang and Youliang Zhao
Polymer Chemistry 2012 vol. 3(Issue 7) pp:1803-1812
Publication Date(Web):02 Dec 2011
DOI:10.1039/C1PY00396H
A facile strategy for synthesizing highly pure block copolymers with polymeric segments such as polystyrene, polyacrylamides and polyacrylates was described. The methodology involves a grafting reaction by tandem RAFT polymerization and azide–alkyne cycloaddition reaction and a subsequent de-grafting reaction via aminolysis or radical-induced addition-fragmentation reaction. S-methoxycarbonylphenylmethyl S′-propynyloxycarbonylethyltrithiocarbonate was used to synthesize Z-alkyne-functionalized macro chain transfer agents, and silica particles grafted with well-defined “living” block copolymers were obtained by simultaneous RAFT process and click reaction using clickable RAFT agents and azido-functionalized silica particles as raw materials. This approach afforded grafted polymers with polydispersity typically lower than 1.2 and silica–polymer hybrids with grafting density in the range of 0.020–0.091 chains nm−2 as the grafted chains had molecular weights between 4920 and 26300 g mol−1. Highly pure block copolymers with terminal functionalities such as thiol, methyldithio, carboxyl, hydroxyl and halogen were obtained by a de-grafting process and postmodification, and azido-functionalized silica particles were efficiently recovered. The cycles of grafting and de-grafting reactions could be applied many times, and no significant decrease in grafting density was noted, indicating the versatility and generality of this approach for surface modification, synthesis of high-purity block copolymers and recycling of clickable solid substrate.
Co-reporter:Shixian Li;Chunnuan Ye;Guangdong Zhao;Meijing Zhang
Journal of Polymer Science Part A: Polymer Chemistry 2012 Volume 50( Issue 15) pp:3135-3148
Publication Date(Web):
DOI:10.1002/pola.26100
Abstract
Symmetric reduction-responsive amphiphilic comblike copolymers mid-disulfide-functionalized comblike copolymers with alternating copolymer comprised of styrenic unit and N-(2-hydroxyethyl) maleimide (HEMI) unit (poly(St-alt-HEMI)) backbones and alternating PEG and PCL side chains (S-CP(PEG-alt-PCL)) with poly(St-alt-HEMI) backbones and alternating poly(ε-caprolactone) (PCL) and poly(ethylene glycol) (PEG) side chains were synthesized and used as nanocarriers for in vitro release of doxorubicin. The target copolymers with predetermined molecular weight and narrow molecular weight distribution (Mw/Mn = 1.15–1.20) were synthesized by reversible addition-fragmentation chain transfer (RAFT) copolymerization of vinylbenzyl-terminated PEG and N-(2-hydroxyethyl) maleimide mediated by a disulfide-functionalized RAFT agent S-CPDB, and followed by ring-opening polymerization of ε-caprolactone. When compared with linear block copolymer comprised of poly(ethylene glycol) (PEG) and poly(ϵ-caprolactone) (PCL) segments (PEG-b-PCL) copolymers, comblike copolymers with similar PCL contents usually exhibited decreased crystallization temperature, melting temperature, and degree of crystallinity, indicating the significant influence of copolymer architecture on physicochemical properties. Dynamic light scattering measurements revealed that comblike copolymers were liable to self-assemble into aggregates involving vesicles and micelles with average diameter in the range of 56–226 nm and particle size distribution ranging between 0.07 and 0.20. In contrast to linear copolymer aggregates, comblike copolymer aggregates with similar compositions were of improved storage stability and enhanced drug-loading efficiency. In vitro drug release confirmed the disulfide-linked comblike copolymer aggregates could rapidly release the encapsulated drug when triggered by 10 mM DL-dithiothreitol. These reduction-sensitive, biocompatible, and biodegradable aggregates have a potential as controlled delivery vehicles. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012
Co-reporter:Huanhuan Liu;Shixian Li;Meijing Zhang;Wei Shao
Journal of Polymer Science Part A: Polymer Chemistry 2012 Volume 50( Issue 22) pp:4705-4716
Publication Date(Web):
DOI:10.1002/pola.26285
Abstract
A facile approach to synthesis of ABCDE-type H-shaped quintopolymer comprising polystyrene (PSt, C) main chain and poly(ethylene glycol) (PEG, A), poly(ε-caprolactone) (PCL, B), poly(L-lactide) (PLLA, D), and poly(acrylic acid) (PAA, E) side chains was described, and physicochemical properties and potential applications as drug carriers of copolymers obtained were investigated. Azide-alkyne cycloaddition reaction and hydrolysis were used to synthesize well-defined H-shaped quintopolymer. Cytotoxicity studies revealed H-shaped copolymer aggregates were nontoxic and biocompatible, and drug loading and release properties were affected by macromolecular architecture, chemical composition, and pH value. The release rate of doxorubicin from copolymer aggregates at pH 7.4 was decreased in the order PAA-b-PLLA > H-shaped copolymer > PEG-PCL-PSt star, and the release kinetics at lower pH was faster. The H-shaped copolymer aggregates have a potential as controlled delivery vehicles due to their excellent storage stability, satisfactory drug loading capacity, and pH-sensitive release rate of doxorubicin. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012
Co-reporter:Kun Jiang, Chunnuan Ye, Peipei Zhang, Xiaosong Wang, and Youliang Zhao
Macromolecules 2012 Volume 45(Issue 3) pp:1346-1355
Publication Date(Web):January 20, 2012
DOI:10.1021/ma2024655
An original strategy is presented to synthesize homopolymers and diblock copolymers grafted graphene oxide by simultaneous coupling reaction and RAFT process. Z-functionalized S-methoxycarbonylphenylmethyl S′-3-(trimethoxysilyl)propyltrithiocarbonate (MPTT) and R-functionalized S-4-(trimethoxysilyl)benzyl S′-propyltrithiocarbonate (TBPT) were used as couplable RAFT agents to prepare the target nanocomposites. Under similar conditions, MPTT-mediated grafting reaction was liable to afford grafted chains with shorter chain length, narrower molecular weight distribution and lower grafting density than TBPT-based reaction owing to increased shielding effect and different grafting process. The grafted polymers had nearly controlled molecular weight and polydispersity ranging between 1.11 and 1.38, and the apparent molar grafting ratio was estimated to be 73.6–220 μmol/g as the molecular weights of grafted polymers were in the range of 3980–12500 g/mol. The improved solubility and dispersibility of GO–polymer composites in various solvents comprising hexane and water confirmed their amphiphilicity. The grafting process offers an opportunity to alter GO morphologies, and surface morphologies involving nanosheets, nanoparticles, and nanorods were observed as the composites were dispersed in different solvents with the aid of sonication treatment. This tandem approach is promising for surface modification of solid substrates with hydroxyl surface due to its mild conditions, straightforward synthesis and good controllability.
Co-reporter:Chunnuan Ye, Guangdong Zhao, Meijing Zhang, Jianzhong Du, and Youliang Zhao
Macromolecules 2012 Volume 45(Issue 18) pp:7429-7439
Publication Date(Web):September 7, 2012
DOI:10.1021/ma3015118
A facile approach based on integrated utilization of ring-opening polymerization (ROP), reversible addition–fragmentation chain transfer (RAFT) process, and azide–alkyne cycloaddition reaction was efficiently used to construct amphiphilic 5-arm ABCDE star quintopolymers. The miktoarm stars are composed of poly(ethylene glycol) (A), poly(ε-caprolactone) (B), polystyrene (C), poly(l-lactide) (D), poly(N,N-dimethylaminoethyl methacrylate) (E1), poly(methyl methacrylate) (E2), and poly(methyl acrylate) (E3). Alkyne-in-chain-functionalized BC and DE diblock copolymers were synthesized by successive ROP and RAFT process. Selective [3 + 2] click reaction between two-azide-end-functionalized PEG and BC copolymer gave azide-core-functionalized ABC star terpolymer, and a subsequent click reaction with DE copolymer afforded well-defined ABCDE stars with well-controlled molecular weight, low polydispersity, and precise composition, as evidenced from 1H NMR, GPC, and GPC-MALLS analyses. DSC analyses revealed part of polymer segments in ABCDE stars were compatible. This general methodology has some advantages such as straightforward synthesis, mild reaction conditions, versatile polymerizable monomers, and high yields, which is promising for the construction of numerous functional star copolymers with multiple compositions and precise microstructures.
Co-reporter:Meijing Zhang, Huanhuan Liu, Wei Shao, Chunnuan Ye, and Youliang Zhao
Macromolecules 2012 Volume 45(Issue 23) pp:9312-9325
Publication Date(Web):November 16, 2012
DOI:10.1021/ma301973v
Menschutkin reaction and controlled polymerization were combined to construct three types of star polymers with a branched core. Branched PVD was synthesized by reversible addition–fragmentation chain transfer (RAFT) copolymerization and used as a core reagent to synthesize multiarm and miktoarm stars with poly(ε-caprolactone) (PCL), polystyrene, poly(methyl methacrylate), poly(tert-butyl acrylate), and poly(N-isopropylacrylamide) segments. Effects of reaction time, feed ratio, and arm length on coupling reaction between PVD and bromide-functionalized polymer were investigated, and a variety of Am-type stars (m ≈ 7.0–35.1) were obtained. Meanwhile, AmBn stars (m ≈ 9.0, n ≈ 6.1–11.3) were achieved by successive Menschutkin reactions, and AmCo stars (m ≈ 8.8–9.0, o ≈ 5.0) were generated by tandem quaternization and RAFT processes. Molecular weights of various stars usually agreed well with the theoretical values, and their polydispersity indices were in the range of 1.06–1.24. The arm number, chain length, and chemical composition of star polymers could be roughly adjusted by control over reaction conditions and utilization of alternative methods, revealing the generality and versatility of these approaches. These ion-bearing stars were liable to exhibit solubility different from normal covalently bonded polymers, and the chain relaxation and melting behaviors of polymer segments were strongly dependent on the macromolecular architecture.
Co-reporter:Peipei Zhang, Kun Jiang, Chunnuan Ye and Youliang Zhao
Chemical Communications 2011 vol. 47(Issue 33) pp:9504-9506
Publication Date(Web):18 Jul 2011
DOI:10.1039/C1CC12978C
Mid-functionalized ABC triblock copolymers with a short central B block were synthesized via the RAFT process, and further used as well-defined V-shaped copolymers to graft onto graphene oxide by coupling reactions.
Co-reporter:Chengbo Zhang, Yuan Zhou, Qiang Liu, Shixian Li, Sébastien Perrier, and Youliang Zhao
Macromolecules 2011 Volume 44(Issue 7) pp:2034-2049
Publication Date(Web):March 11, 2011
DOI:10.1021/ma1024736
Facile synthesis of hyperbranched and star polymers on the basis of S-(4-vinyl)benzyl S′-propyltrithiocarbonate (VBPT) was described. RAFT copolymerization of VBPT with vinyl monomers such as methyl methacrylates (MMA), styrene (St), methyl acrylate (MA), and tert-butyl acrylate (tBA) afforded hyperbranched copolymers with variable branch length and degree of branching. Hyperbranched copolymers obtained at a low feed ratio of vinyl monomers to VBPT usually possessed repeat units per branch higher than the expected values due to the presence of VBPT unit with pendant trithiocarbonate group and side reactions resulting in partial loss of CTA functionality. RAFT copolymerization at various feed ratios afforded poly(VBPT-co-MA) branched copolymers with weight-average CTA functionality up to 107 or more, which were further used to generate star PSt and PtBA with adjustable molecular weight and variable polydispersity (1.12 < PDI < 1.88). The approach based on two successive RAFT processes is general and versatile to synthesize multiarm star polymers with controllable arm length. The resultant polymers were characterized by 1H NMR, GPC-MALLS, DSC, and TGA. The intrinsic viscosities of branched and star-shaped polymers were lower than those of their linear analogues with the same molecular weights; both Mark−Houwink−Sakurada exponent and contractor factor of branched copolymers were observed to increase with decreasing degree of branching, thus confirming a branching nature. The single glass transition temperature in DSC traces indicated branched copolymers obtained at various feed ratios had good compatibility.
Co-reporter:Chunnuan Ye;Weina Qi;Xinhua Yu;Peipei Zhang
Frontiers of Chemistry in China 2011 Volume 6( Issue 3) pp:
Publication Date(Web):2011 September
DOI:10.1007/s11458-011-0253-6
This study aimed at the synthesis of silica particles grafted with better-defined homopolymers and block copolymers by tandem approach. Z-functionalized S-benzyl S′-(3-trimethoxysilyl)propyltrithiocarbonate (BTPT) was used as a couplable RAFT agent to synthesize the target inorganic-organic hybrids. Simultaneous coupling reaction and RAFT process using silica particles and BTPT as raw materials efficiently afforded homopolymers grafted silica, and RAFT-synthesized macro chain transfer agents with ω-terminal trimethoxysilane moiety were utilized to mediate graft reaction to prepare silica particles grafted with di-, tri- and tetrablock copolymers comprised of polymer segments such as polystyrene, polyacrylamides and polyacrylates. When the grafted chains had molecular weights ranging between 3920 and 24800 g/mol, the molar grafting ratios, which were dependent on reaction conditions and types and compositions of grafted chains, were estimated to be in the range of 15.2–101 μmol/g, and grafted polymers usually had polydispersity indices lower than 1.3, revealing that the grafting process was almost controllable. To the best of our knowledge, this versatile tandem approach is one of the most facile techniques to prepare silica particles grafted with polymeric chains with controlled molecular weight, low polydispersity and precise composition due to its minimal reaction steps, mild conditions, straightforward synthesis and satisfactory controllability.
Co-reporter:Tengteng Hou, Peipei Zhang, Xiangdong Zhou, Xiangqian Cao and Youliang Zhao
Chemical Communications 2010 vol. 46(Issue 39) pp:7397-7399
Publication Date(Web):07 Sep 2010
DOI:10.1039/C0CC02135K
Radical-induced addition–fragmentation processes were efficiently used for surface modification of fumed silica, and Z-supported solid CTAs could be reused in presence of excess sacrificial thermal initiator.
Co-reporter:Youke Huang, Tengteng Hou, Xiangqian Cao, Sébastien Perrier and Youliang Zhao
Polymer Chemistry 2010 vol. 1(Issue 10) pp:1615-1623
Publication Date(Web):31 Aug 2010
DOI:10.1039/C0PY00165A
An original strategy is presented to synthesize highly pure multiblock copolymers (up to tetrablock) of various monomers tethered to silica particles, by combining RAFT polymerization and click chemistry. Two approaches were compared that follow this strategy. In a first approach, Z-azide-functionalized polymers were prepared via a RAFT process and then tethered to silica particles via a direct click reaction. This approach led to well-defined grafted polymers with polydispersity indices lower than their “as-prepared” precursors, due to lack of dead chains. In a second approach, a one-pot method was employed, using clickable RAFT agents to perform RAFT polymerization and click reaction simultaneously. This route afforded grafted polymers with polydispersity typically less than 1.25, whilst the chain length of grafted polymers was usually shorter than that of free polymers formed in solution, due to shielding effect and heterogeneous reaction condition. A series of well-defined homopolymers, di-, tri- and tetrablock copolymers could be efficiently grafted onto silica particles, and the grafting density was usually ranged between 0.017 and 0.085 chains nm−2, evident from GPC, IR, elemental and thermogravimetric analyses. The one-pot approach seems more promising than the incremental route, since it is a one step reaction that still maintains controllability over surface modification.
Co-reporter:Qiang Liu;You-ke Huang;Xiang-dong Zhou
Chinese Journal of Polymer Science 2010 Volume 28( Issue 5) pp:819-828
Publication Date(Web):2010 September
DOI:10.1007/s10118-010-9166-y
A series of 3-arm ABC and AA′B and 4-arm ABCD, AA′BC and AA′A″B heteroarm star polymers comprising one poly(4-methylphenyl vinyl sulfoxide) segment and other segments such as polystyrene, poly(α-methylstyrene), poly(4-methoxystyrene) and poly(4-trimethylsilylstyrene) were synthesized by living anionic polymerization based on diphenylethylene (DPE) chemistry. The DPE-functionalized polymers were synthesized by iterative methodology, and the objective star polymers were prepared by two distinct methodologies based on anionic polymerization using DPE-functionalized polymers. The first methodology involves an addition reaction of living anionic polymer with excess DPE-functionalized polymer and a subsequent living anionic polymerization of 4-methylphenyl vinyl sulfoxide (MePVSO) initiated from the in situ formed polymer anion with two or three polymer segments. The second methodology comprises an addition reaction of DPE-functionalized polymer with excess sec-BuLi and a following anionic polymerization of MePVSO initiated from the in situ formed polymer anion and 3-methyl-1,1-diphenylpentyl anion as well. Both approaches could afford the target heteroarm star polymers with predetermined molecular weight, narrow molecular weight distribution (Mw/Mn < 1.03) and desired composition, evidenced by SEC, 1H-NMR and SLS analyses. These polymers can be used as model polymers to investigate structure-property relationships in heteroarm star polymers.
Co-reporter:Xiao Jiang, Meijing Zhang, Shixian Li, Wei Shao and Youliang Zhao
Chemical Communications 2012 - vol. 48(Issue 79) pp:NaN9908-9908
Publication Date(Web):2012/08/13
DOI:10.1039/C2CC35275C
A straightforward strategy involving a RAFT process and ring-opening polymerization was used to construct symmetric reduction-responsive amphiphilic A2mB2nC2 (m ≈ n ≈ 3) starlike terpolymers with precise microstructure, which could be efficiently converted into thiol-functionalized telechelic stars, degraded AmBnC miktoarm stars and comblike-linear multiblock copolymers via postmodification.
Co-reporter:Peipei Zhang, Kun Jiang, Chunnuan Ye and Youliang Zhao
Chemical Communications 2011 - vol. 47(Issue 33) pp:NaN9506-9506
Publication Date(Web):2011/07/18
DOI:10.1039/C1CC12978C
Mid-functionalized ABC triblock copolymers with a short central B block were synthesized via the RAFT process, and further used as well-defined V-shaped copolymers to graft onto graphene oxide by coupling reactions.
Co-reporter:Tengteng Hou, Peipei Zhang, Xiangdong Zhou, Xiangqian Cao and Youliang Zhao
Chemical Communications 2010 - vol. 46(Issue 39) pp:NaN7399-7399
Publication Date(Web):2010/09/07
DOI:10.1039/C0CC02135K
Radical-induced addition–fragmentation processes were efficiently used for surface modification of fumed silica, and Z-supported solid CTAs could be reused in presence of excess sacrificial thermal initiator.
Co-reporter:Huanhuan Liu, Cangxia Li, Dandan Tang, Xiaonan An, Yanfei Guo and Youliang Zhao
Journal of Materials Chemistry A 2015 - vol. 3(Issue 19) pp:NaN3971-3971
Publication Date(Web):2015/04/17
DOI:10.1039/C5TB00473J
Thermo-, pH and reduction triggered drug delivery vehicles based on dual-cleavable polymeric micelles were investigated. A comblike copolymer (G3) comprising one disulfide linkage and PEG, PCL and acetal-bridged PCL-b-PNIPAM grafts was controllably synthesized by successive RAFT copolymerization, ring-opening polymerization and adductive reaction. G3 was liable to self-assemble into spherical micelles at 25 °C and toroidal micelles at 37 °C, and the aggregates formed at 37 °C could be further converted into multicompartment micelles (pH 5.3), spherical micelles (DTT) and hyperbranched or necklace-like cylinders (pH 5.3 + DTT) upon external stimuli due to the stimuli-triggered topological transformation and reaggregation of copolymer aggregates. Upon external stimuli, doxorubicin (DOX) loaded G3 and G3/β-CD (co)aggregates could exhibit accelerated drug release kinetics. The apparent release rates varied in the range 0.072–0.403 h−1 (for G3 aggregates) and 0.142–0.458 h−1 (for G3/β-CD coaggregates), revealing that the drug release system bearing host–guest interactions could further extend the ranges of the release rate and cumulative release. Although β-CD and G3 micelles lacked notable cytotoxicity, the cytotoxicity of DOX-loaded (co)aggregates to 4T1 cells was higher than free DOX. CLSM images revealed that DOX-loaded copolymer aggregates may enter cells via endocytosis in a manner of nanocomplexes. Our study can not only extend the potential of stimuli-cleavable copolymers toward biomedical applications but also enrich the family of multi-responsive copolymer aggregates.
Co-reporter:Youke Huang ; Qiang Liu ; Xiangdong Zhou ; Sébastien Perrier
Macromolecules () pp:
Publication Date(Web):July 17, 2009
DOI:10.1021/ma900604v
A combinatorial approach based on reversible addition−fragmentation chain transfer (RAFT) polymerization and coupling reaction was used to prepare well-defined silica−polymer hybrids. Chain-end-functionalized homopolymers were synthesized by RAFT polymerization of vinyl monomers such as methyl acrylate, butyl acrylate, N,N-dimethylacrylamide, N-isopropylacrylamide, N-acrylomorpholine, methyl methacrylate, and styrene mediated by S-methoxycarbonylphenylmethyl S′-trimethoxysilylpropyltrithiocarbonate in toluene or dioxane at 60 °C, and di-, tri-, and tetrablock copolymers were further synthesized by successive chain extension polymerization. These polymers comprising a trimethoxysilane functionality in the chain end were then grafted to the surface of flash silica by coupling reaction between trimethoxysilane and hydroxyl groups. IR and thermogravimetric analyses results indicated the grafting ratios of polymeric chains on the surface of silica were relatively high. The grafted polymeric chains were cleaved from the surface of silica by aminolysis, and gel permeation chromatography results revealed all the grafted polymers possessed low polydispersity (typically less than 1.2) and molecular weight similar to that of the “as-prepared” polymers. Furthermore, the solid-supported polymeric chains were almost 100% living, evident from highly efficient chain extension polymerization to prepare well-defined block copolymers grafted onto silica particles.
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![Pentanoic acid, 4-cyano-4-[(phenylthioxomethyl)thio]-, 2-[[2-[(1-oxo-2-propen-1-yl)oxy]ethyl]dithio]ethyl ester](/data/chemimg/3781700/1421969-30-3.png)
![Pentanoic acid, 4-cyano-4-[(phenylthioxomethyl)thio]-, 2-[[2-[(1-oxo-2-propen-1-yl)oxy]ethyl]dithio]ethyl ester](/data/chemimg/3781700/1421969-30-3_b.png)
![Pentanoic acid, 4-cyano-4-[(phenylthioxomethyl)thio]-, 2-[(2-hydroxyethyl)dithio]ethyl ester](/data/chemimg/3781700/1421969-29-0.png)
![Pentanoic acid, 4-cyano-4-[(phenylthioxomethyl)thio]-, 2-[(2-hydroxyethyl)dithio]ethyl ester](/data/chemimg/3781700/1421969-29-0_b.png)
![Pentanoic acid, 4-cyano-4-[(phenylthioxomethyl)thio]-, 3-bromopropyl ester](/data/chemimg/3781700/1414117-60-4.png)
![Pentanoic acid, 4-cyano-4-[(phenylthioxomethyl)thio]-, 3-bromopropyl ester](/data/chemimg/3781700/1414117-60-4_b.png)
![Pentanoic acid, 4-cyano-4-[(phenylthioxomethyl)thio]-, 2-(hydroxymethyl)-2-methyl-3-oxo-3-(2-propyn-1-yloxy)propyl ester](/data/chemimg/3723500/1399854-65-9.png)
![Pentanoic acid, 4-cyano-4-[(phenylthioxomethyl)thio]-, 2-(hydroxymethyl)-2-methyl-3-oxo-3-(2-propyn-1-yloxy)propyl ester](/data/chemimg/3723500/1399854-65-9_b.png)
![Pentanoic acid, 4-cyano-4-[(phenylthioxomethyl)thio]-, 2-propyn-1-yl ester](/data/chemimg/190000/1075252-15-1.png)
![Pentanoic acid, 4-cyano-4-[(phenylthioxomethyl)thio]-, 2-propyn-1-yl ester](/data/chemimg/190000/1075252-15-1_b.png)
![Carbonotrithioic acid, phenylmethyl [3-(trimethoxysilyl)propyl] ester](/data/chemimg/3730200/1000290-88-9.png)
![Carbonotrithioic acid, phenylmethyl [3-(trimethoxysilyl)propyl] ester](/data/chemimg/3730200/1000290-88-9_b.png)
![Poly[oxy[(1S)-1-methyl-2-oxo-1,2-ethanediyl]]](http://img.cochemist.com/ccimg/26200/26161-42-2.png)
![Poly[oxy[(1S)-1-methyl-2-oxo-1,2-ethanediyl]]](http://img.cochemist.com/ccimg/26200/26161-42-2_b.png)
![Pentanoic acid, 4-?cyano-?4-?[(phenylthioxomethyl?)?thio]?-?, 1,?1'-?(dithiodi-?2,?1-?ethanediyl) ester](/data/chemimg/3781300/1402089-91-1.png)
![Pentanoic acid, 4-?cyano-?4-?[(phenylthioxomethyl?)?thio]?-?, 1,?1'-?(dithiodi-?2,?1-?ethanediyl) ester](/data/chemimg/3781300/1402089-91-1_b.png)
![Poly[oxy(1-oxo-1,6-hexanediyl)]](http://img.cochemist.com/ccimg/25300/25248-42-4.png)
![Poly[oxy(1-oxo-1,6-hexanediyl)]](http://img.cochemist.com/ccimg/25300/25248-42-4_b.png)
