Guolin Wu

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Name: 伍国琳; GuoLin Wu

Organization: Nankai University , China

Department: Institute of Polymer Chemistry

Title: Associate Professor(PhD)

TOPICS

Polymer

Stimuli Responsive Polymers PH Responsive Polymers Stimuli Responsive Polymers PH Responsive Polymers Temperature Responsive Polymers

Material Chemistry

Organic Chemistry

Peptide Synthesis

Chemicals
References

A magnetic polypeptide nanocomposite with pH and near-infrared dual responsiveness for cancer therapy

Co-reporter:Jie Zhang;Chu Gong;Bingqiang Li;Meng Shan

Journal of Polymer Research 2017 Volume 24( Issue 8) pp:122

Publication Date(Web):17 July 2017

DOI:10.1007/s10965-017-1277-5

A magnetic polypeptide nanocomposite with pH and near-infrared (NIR) dual responsiveness was developed as a drug carrier for cancer therapy, which was prepared through the self-assembly of Fe3O4 superparamagnetic nanoparticles, poly(aspartic acid) derivative (mPEG-g-PDAEAIM) and doxorubicin (DOX) in water. Fe3O4 nanoparticles were prepared to provide the superparamagnetic core of nanocomposites for tumor targeting via chemical co-precipitation. The protonable imidazole groups of mPEG-g-PDAEAIM with a pKa of ~7 were accountable for the pH-responsiveness of nanocomposites. The photothermal effect of nanocomposites under the irradiation of NIR laser was induced via the interactions between dopamine groups of mPEG-g-PDAEAIM and Fe3O4 superparamagnetic nanoparticles to trigger the drug release. NMR, FT-IR, TEM, hysteresis loop analysis and MRI were utilized to characterize the materials. The DOX loaded nanocomposites exhibited pH-responsive and NIR dependent on/off switchable release profiles. The nanocomposites without drug loading (Fe3O4@mPEG-g-PDAEAIM) showed excellent biocompatibility while DOX loaded nanocomposites caused MCF-7 cells’ apoptosis due to the photothermal/chemotherapy combination effects. Overall, the pH and near-infrared dual responsive magnetic nanocomposite had a great potential for cancer therapy.

A dual pH- and reduction-responsive anticancer drug delivery system based on PEG–SS–poly(amino acid) block copolymer

Co-reporter:Bingqiang Li;Meng Shan;Xiang Di;Chu Gong;Lihua Zhang;Yanming Wang

RSC Advances (2011-Present) 2017 vol. 7(Issue 48) pp:30242-30249

Publication Date(Web):2017/06/08

DOI:10.1039/C7RA04254J

A pH- and reduction-responsive anticancer drug delivery system was prepared and the triggerable and controllable drug release in response to stimuli was observed. In the first step, methoxy-poly(ethylene glycol) (mPEG) was conjugated with polysuccinimide (PSI) via disulfide linkages, and the PSI segment thereafter, was aminolyzed by 2-diisopropylaminoethylamine (DIPEA) and hydrazine hydrate (Hy). The obtained amphiphilic copolymer could form a bond with the model drug doxorubicin (DOX) at pH 7.4 via acid-labile hydrazone bonds, and more free DOX molecules could be encapsulated via hydrophobic interactions and π–π stacking between the aromatic rings, leading to DOX-loaded micelles formation. These polymers and polymeric micelles then were characterized. The results showed that the polymeric micelles exhibited dual pH- and reduction-responsive disassembly behaviors. Moreover, while the blank copolymers had excellent cytocompatibility, the DOX-loaded micelles showed an enhanced drug release profile and improved cytotoxicity with decrease of pH and/or the addition of glutathione (GSH). These results indicated that the novel nanoparticle based on PEG–SS–poly(amino acid) block copolymer is a promising candidate for a carrier in controllable anti-tumor drug delivery.

A pH, glucose, and dopamine triple-responsive, self-healable adhesive hydrogel formed by phenylborate–catechol complexation

Co-reporter:Meng Shan;Chu Gong;Bingqiang Li

Polymer Chemistry (2010-Present) 2017 vol. 8(Issue 19) pp:2997-3005

Publication Date(Web):2017/05/16

DOI:10.1039/C7PY00519A

An injectable polyethylene glycol (PEG) hydrogel was successfully prepared via borate–catechol complexation using dopamine functionalized 4-armed PEG (4-arm-PEG-DA) and phenylboronic acid modified 4-armed PEG (4-arm-PEG-PBA). The hydrogel was formed within 10 s by mixing 15 wt% 4-arm-PEG-DA with 15 wt% 4-arm-PEG-PBA buffer solutions at pH 9.0. The hydrogel was characterized by Fourier transform infrared (FT-IR) spectroscopy, rheological measurements, scanning electron microscopy (SEM) and lap shear strength tests. Furthermore, pH, glucose and dopamine responsiveness of the hydrogel based on phenylborate–catechol complexation was demonstrated by degradation experiments and drug release tests. The lap shear strength tests indicated that the hydrogel possessed the ability of self-healing which was bestowed by the phenylborate–catechol dynamic covalent bond. Moreover, the hydrogel could serve as a decent bio-adhesive due to its adhesion properties on different substrates especially the porcine skin. In vitro cytotoxicity tests demonstrated the excellent cytocompatibility of the hydrogel. The results of all the experiments indicate that our newly developed multi-functionalized hydrogel can have potential applications in biomedical fields such as drug delivery, tissue engineering, and bio-adhesives.

Dopamine-modified poly(amino acid): an efficient near-infrared photothermal therapeutic agent for cancer therapy

Co-reporter:Chu Gong;Caicai Lu;Bingqiang Li;Meng Shan

Journal of Materials Science 2017 Volume 52( Issue 2) pp:955-967

Publication Date(Web):14 September 2016

DOI:10.1007/s10853-016-0391-9

Under the inspiration of polydopamine melanin, a new dopamine-modified poly(aspartic acid) derivative, poly(α,β-(N-(3,4-dihydroxyphenylethyl)-l-aspartamide-co-α,β-N-(2-hydroxyethyl)-l-aspartamide) (PDAEA), was successfully synthesized by successive aminolysis reactions of polysuccinimide with dopamine and ethanolamine. The mixtures composed of PDAEA and FeCl3 exhibited an excellent photothermal property under the irradiation of near-infrared (NIR) laser. The interactions between PDAEA and FeCl3 were investigated by ultraviolet–visible (UV–Vis) spectroscopic, Fourier transformation infrared (FT-IR) spectroscopic, and visual colorimetric measurements. Additionally, PDAEA could interact with Fe3+ in water to form spherical nanostructures with a size of 116 nm, apt to aggregate at the tumor site via the enhanced permeability and retention effect (EPR effect), implying that toxic and side effects of traditional therapy might be reduced using this method. MTT assay demonstrated both PDAEA and the obtained complex products possessed good cytocompatibility to NIH-3T3 cells (more than 90 % cell viability). The effect of photothermal therapy in vitro was also evaluated qualitatively under certain conditions using an inverted fluorescence microscope. All the results indicated that the dopamine-modified poly(aspartic acid) derivative was a promising candidate as an efficient NIR photothermal therapeutic agent for cancer therapy.

Crosslinkable polyesters based on monomers derived from renewable lignin

Co-reporter:Jie Zhang, Chengcai Pang and Guolin Wu

RSC Advances 2016 vol. 6(Issue 14) pp:11848-11854

Publication Date(Web):22 Jan 2016

DOI:10.1039/C5RA26155D

Crosslinked polyesters were successfully prepared using thiol-ene click chemistry. Vanillic acid, syringic acid, and p-hydroxybenzoic acid have similar aromatic structures. They can be derived from a renewable resource, lignin. In this paper, they were used as raw materials for the synthesis of unsaturated thermoplastic polyesters, by polycondensation in solvent. The obtained polyesters were characterized by FTIR and NMR, and their tensile properties were tested. Compared to the other two unsaturated polyesters, the vanillic acid based unsaturated polyester (P1) was found to have the best tensile property. The latter was chosen for the preparation of the crosslinked polyester and further studies were carried out. Differential scanning calorimetry (DSC) revealed an amorphous character of P1, having a Tg of 35.8 °C. Thermogravimetric analysis (TGA) and tensile tests were conducted to study the thermal and mechanical properties of P1 and the crosslinked polyesters. The weight-average molecular weight (Mw) of P1 was found to be 73000 g mol−1. The unsaturated bonds in the polymers were found to have a special feature, which improved the flexibility of the polyesters on crosslinking. Moreover, both the unsaturated polyesters and the crosslinked polyesters were found to be biodegradable.

pH-responsive zwitterionic polypeptide as a platform for anti-tumor drug delivery

Co-reporter:Na Liu, Jiaming Han, Xinchen Zhang, Yue Yang, Yuan Liu, Yanming Wang, Guolin Wu

Colloids and Surfaces B: Biointerfaces 2016 Volume 145() pp:401-409

Publication Date(Web):1 September 2016

DOI:10.1016/j.colsurfb.2016.05.027

•Nanoparticles based on poly(amino acid)s.•Modified with zwitterionic lysine groups as the hydrophilic segments.•DOX loaded via cleavable hydrazone bonds, hydrophobic interaction and π-π stacking.•A pH-dependent drug release profile.•Particles with surface charge conversion at different pH.In this paper, a doxorubicin delivery system is reported based on a pH-responsive zwitterionic polypeptide derivative. To improve the anti-protein-fouling capacity, the poly(amino acid) was modified by grafting short-chain zwitterions via aminolysis reaction of polysuccinimide with l-lysine. As a result, both positively and negatively charged moieties were introduced onto the same side chain in a simultaneous fashion, providing a nano-scale homogenous mixture of balanced charges. The zwitterionic side chains serve as hydrophilic segments in the copolymer and feature excellent resistance to nonspecific protein adsorption. Doxorubicin was chemically grafted onto the poly(amino acid) moiety through acid-labile hydrazone linkages, providing removable hydrophobic segments and driving the polymer self-assembly. Free doxorubicin could be encapsulated into the self-assembled micelles via hydrophobic interactions and molecular π-π stacking. The results obtained show that the drug loaded nanoparticles exhibit excellent stabilities in protein solutions at pH = 7.4 and significantly enhanced drug release characteristics under acidic conditions. The cytotoxicity characteristics of the zwitterionic copolymer and drug-loaded nanoparticles at different pH values were investigated in vitro and feature an excellent biocompatibility and anti-cancer activity, respectively.

A pH and redox dual stimuli-responsive poly(amino acid) derivative for controlled drug release

Co-reporter:Chu Gong, Meng Shan, Bingqiang Li, Guolin Wu

Colloids and Surfaces B: Biointerfaces 2016 Volume 146() pp:396-405

Publication Date(Web):1 October 2016

DOI:10.1016/j.colsurfb.2016.06.038

•A polymeric micelle drug carrier based on a poly(aspartic acid) derivative.•Excellent biocompatibility and biodegradability.•Convenient and simple synthesis and modification.•pH and redox dual stimuli-responsive drug release profiles.•A very little leakage of drugs at pH 7.4.A pH and redox dual stimuli-responsive poly(aspartic acid) derivative for controlled drug release was successfully developed through progressive ring-opening reactions of polysuccinimide (PSI). Polyethylene glycol (PEG) chains were grafted onto the polyaspartamide backbone via redox-responsive disulfide linkages, providing a sheddable shell for the polymeric micelles in a reductive environment. Phenyl groups were introduced into the polyaspartamide backbone via the aminolysis reaction of PSI to serve as the hydrophobic segment of micelles. The polyaspartamide scaffold was also functionalized with N-(3-aminopropyl)-imidazole to obtain the pH-responsiveness manifesting as a swelling of the core of micelles at a low pH. The polymeric micelles with a core-shell nanostructure forming in neutral media exhibited both pH and redox responsive characteristics. Doxorubicin (DOX) as a model drug was encapsulated into the core of micelles through both hydrophobic and π-π interactions between aromatic rings and the DOX-loaded polymeric micelles exhibited accelerated drug release behaviors in an acidic and reductive environment due to the swelling of hydrophobic cores and the shedding of PEG shells. Furthermore, the cytocompability of the polymer and the cytotoxicity of DOX-loaded micelles towards Hela cells under corresponding conditions were evaluated, and the endocytosis of DOX-loaded polymeric micelles and the intracellular drug release from micelles were observed. All obtained data indicated that the micelle was a promising candidate for controlled drug release.

PH responsive polypeptide based polymeric micelles for anticancer drug delivery

Co-reporter:Dongping Zhao;Bingqiang Li;Jiaming Han;Yue Yang;Xinchen Zhang

Journal of Biomedical Materials Research Part A 2015 Volume 103( Issue 9) pp:3045-3053

Publication Date(Web):

DOI:10.1002/jbm.a.35434

Abstract

A pH-responsive polymeric micelle based on poly(aspartamide) derivative was explored as an efficient acid-triggered anticancer drug delivery system. Poly(α,β-l-asparthydrazide) (PAHy) was prepared by aminolysis reaction of polysuccinimide with hydrazine hydrate. Poly(ethylene glycol) and aliphatic chain (C18) were conjugated onto PAHy to afford an amphiphilic copolymer with acid-liable hydrazone bonds. The structure of the resulting copolymer and its self-assembled micelles were confirmed by ¹H NMR, FTIR, DLS, and TEM. Furthermore, doxorubicin (DOX) was loaded into the polymeric micelles via the hydrophobic interaction between the C18 group and DOX molecules, and the π-π staking between the hydrazone conjugated DOX and free DOX molecules. Results showed that the DOX loaded nanoparticle (NP) was relatively stable under physiological conditions, while the DOX was quickly released in response to acidity due to the shedding of mPEG shells and dissociating of C18 segments because of the pH-cleavage of intermediate hydrazone bonds. In addition, the DOX loaded micelles presented a high cytotoxic activity against tumor cells in vitro. This pH responsive NP has appeared highly promising for the targeted intracellular delivery of hydrophobic chemotherapeutics in cancer therapy. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 3045–3053, 2015.

Preparation of a multifunctional verapamil-loaded nano-carrier based on a self-assembling PEGylated prodrug

Co-reporter:Dongping Zhao, Na Liu, Kemei Shi, Xiaojuan Wang, Guolin Wu

Colloids and Surfaces B: Biointerfaces 2015 Volume 135() pp:682-688

Publication Date(Web):1 November 2015

DOI:10.1016/j.colsurfb.2015.08.018

•A linear amphiphilic PEGylated prodrug, mPEG-b-DOX has been successfully synthesized by a facile way.•In aqueous solution, the amphiphilic PEG-b-DOX can form stable nanoparticles with a high DOX loading content.•The hydrophilic VRP was loaded into the nano-carriers using a conventional dialysis method.•The dual drug loading nano-carriers exhibited the pH-dependent drug release profiles in vitro.•The combined-system significantly enhanced the cytotoxicity of DOX and induced elevated apoptosis of MCF-7/ADR.In an effort to prove the inherent side effects of doxorubicin (DOX) and potentially revoke the effects of drug resistance exhibited by cancer cells, we have designed a multifunctional DOX-delivery nano-carrier system able to encapsulate the drug resistance reversal agent Verapamil HCl (VRP·HCl). Hydrophilic short-chain polyethylene glycol (i.e., mPEG) was covalently linked to hydrophobic DOX and a benzoic imine linkage was used to form a linear amphiphilic PEGylated prodrug, namely mPEG-b-DOX. In aqueous solution, the amphiphilic PEG-b-DOX is able to self-assemble to form stable nanoparticles with a DOX loading content of approximately 40 wt% and a diameter of ∼143 nm. The resulting nanoparticles can simultaneously serve as an anticancer drug conjugate and as a drug carrier system. Here, the hydrophilic VRP could be encapsulated into the nano-carriers via a conventional dialysis method. The loading efficiency in mPEG-b-DOX nano-carrier was determined to be 53.97% and the loading content was found to be 7.71 wt%. The VRP-loaded nano-carriers grew slightly in size, to a diameter of ∼177 nm. We found that the release of DOX and VRP was much faster at a lower pH value. The biological activity of the nano-carriers were evaluated in vitro and compared with the DOX-loaded system. In doing so we found that the VRP-loaded nano-carrier features a much higher antitumor activity. Furthermore, the combined-system exhibits a significantly enhanced cytotoxicity with an elevated apoptosis rate observed for MCF-7/ADR used as a cell line in this in vitro study. This combinatory system and promising candidate for applications involving DOX chemotherapy proved to be easy to prepare and could be characterized in terms of biocompatibility, biodegradability, loading capacity, pH responsiveness and reversal of drug resistance.

A pH- and thermo-responsive poly(amino acid)-based drug delivery system

Co-reporter:Na Liu, Bingqiang Li, Chu Gong, Yuan Liu, Yanming Wang, Guolin Wu

Colloids and Surfaces B: Biointerfaces 2015 Volume 136() pp:562-569

Publication Date(Web):1 December 2015

DOI:10.1016/j.colsurfb.2015.09.057

•Nanoparticles show sensitivities to both temperature and pH environment.•With a pH-sheddable hydrophilic corona.•DOX was successfully loaded via hydrophobic interaction and π–π stacking.•The drug release profiles displayed a pH and temperature-dependent behavior.•Readily taken up by cells due to shell shedding and the protonation of side tertiary amine groups induced positively charged surface.A pH- and thermo-responsive poly(amino acid)-based amphiphilic copolymer was developed, functioning as a tumour targeting drug delivery system with good biocompatibility and biodegradability. To provide multi-stimuli sensitivity characteristics to the poly(amino acid)s, the polyaspartamide scaffold has been functionalized with N,N-diisopropylamide groups via aminolysis reaction of polysuccinimide. PEG chains have also been chemically grafted to the poly(amino acid) backbone through acid-labile hydrazone linkages, providing a removable shield for the poly(amino acid) based nanoparticles. Furthermore, doxorubicin was chemically linked to the copolymer chain via hydrazone bonds, acting as the hydrophobic moiety to drive the polymeric self-assembly. Free doxorubicin molecules could be encapsulated into the self-assembled nanoparticles via hydrophobic interactions and molecular π–π stacking. The results obtained show that the drug release can be triggered by the temperature with a significantly increased release being observed under acidic conditions. The cytotoxicity behaviour of the copolymers and drug-loaded nanoparticles was investigated in vitro at varying pH values and different temperatures. In doing so, superior characteristics concerning compatibility and anti-cancer activity could be observed.

Controlled Release of Protein from Biodegradable Multi-sensitive Injectable Poly(ether-urethane) Hydrogel

Co-reporter:Xiaomeng Li, Yangyun Wang, Jiaming Chen, Yinong Wang, Jianbiao Ma, and Guolin Wu

ACS Applied Materials & Interfaces 2014 Volume 6(Issue 5) pp:3640

Publication Date(Web):January 24, 2014

DOI:10.1021/am405927f

The synthesis and characterization of multi-sensitive polymers for use as injectable hydrogels for controlled protein/drug delivery is reported. A series of biodegradable multi-sensitive poly(ether-urethane)s were prepared through a simple one-pot condensation of poly(ethylene glycol), 2,2′-dithiodiethanol, N-methyldiethanolamine, and hexamethylene diisocyanate. The sol-gel phase transition behaviors of the obtained copolymers were investigated. Experimental results showed that the aqueous medium comprising the multi-segment copolymers underwent a sol-to-gel phase transition with increasing temperature and pH. At a certain concentration, the copolymer solution could immediately change to a gel under physiological conditions (37 °C and pH 7.4), indicating their suitability as in situ injectable hydrogels in vivo. Insulin was used as a model protein drug for evaluation of the injectable hydrogels as a site-specific drug delivery system. The controlled release of insulin from the hydrogel devices was demonstrated by degradation of the copolymer, which is modulated via the 2,2′-dithiodiethanol content in the poly(ether-urethane)s. These hydrogels having multi-responsive properties may prove to be promising candidates for injectable and controllable protein drug delivery devices.Keywords: biodegradable; drug delivery; injectable; multi-sensitive hydrogels; poly(ether-urethane);

An injectable and biodegradable hydrogel based on poly(,-aspartic acid) derivatives for localized drug delivery

Co-reporter:Caicai Lu;Xiaojuan Wang;Jingjing Wang;Yinong Wang;Hui Gao;Jianbiao Ma

Journal of Biomedical Materials Research Part A 2014 Volume 102( Issue 3) pp:628-638

Publication Date(Web):

DOI:10.1002/jbm.a.34725

Abstract

An injectable hydrogel via hydrazone cross-linking was prepared under mild conditions without addition of cross-linker or catalyst. Hydrazine and aldehyde modified poly(aspartic acid)s were used as two gel precursors. Both of them are water-soluble and biodegradable polymers with a protein-like structure, and obtained by aminolysis reaction of polysuccinimide. The latter can be prepared by thermal polycondensation of aspartic acid. Hydrogels were prepared in PBS solution and characterized by different methods including gel content and swelling, Fourier transformed-infrared spectroscopy, and in vitro degradation experiment. A scanning electron microscope viewed the interior morphology of the obtained hydrogels, which showed porous three-dimensional structures. Different porous sizes were present, which could be well controlled by the degree of aldehyde substitution in precursor poly(aspartic acid) derivatives. The doxorubicin-loaded hydrogels were prepared and showed a pH-sensitive release profile. The release rate can be accelerated by decreasing the environmental pH from a physiological to a weak acidic condition. Moreover, the cell adhesion and growth behaviors on the hydrogel were studied and the polymeric hydrogel showed good biocompatibility. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 628–638, 2014.

Synthesis and characterization of zwitterionic peptides derived from natural amino acids and their resistance to protein adsorption

Co-reporter:Caicai Lu, Dongping Zhao, Shuo Wang, Yanming Wang, Yinong Wang, Hui Gao, Jianbiao Ma and Guolin Wu

RSC Advances 2014 vol. 4(Issue 40) pp:20665-20672

Publication Date(Web):29 Apr 2014

DOI:10.1039/C3RA47353H

Various functional groups can be easily introduced onto the poly(α,β-L-aspartic acid) by using different reagents to open the succinimide ring in polysuccinimide (PSI). In this work, two natural basic amino acids, L-histidine and L-lysine were used as the ring opening reagents to react with PSI. As a result, both positively and negatively charged moieties were introduced onto the same side chain simultaneously, which provides a nano-scale homogenous mixture of balanced charges. The chemical structures of the obtained polymers were confirmed by FT-IR and 1H NMR spectroscopy. Zeta potential and turbidity measurements were applied to investigate the zwitterionic property of the polymers. Substrates pre-coated with the zwitterionic polymers exhibited good hydrophilicity and anti-protein-adsorption ability. What's more, the in vitro cytotoxicity test suggested that these peptide-based zwitterionic materials had good biocompatibility, indicating their good potential as non-fouling materials in the biomedical applications.

Magnetic and pH sensitive drug delivery system through NCA chemistry for tumor targeting

Co-reporter:Jingjing Wang, Chu Gong, Yinong Wang and Guolin Wu

RSC Advances 2014 vol. 4(Issue 31) pp:15856-15862

Publication Date(Web):24 Mar 2014

DOI:10.1039/C4RA00660G

For the purpose of tumor-specific drug delivery applications, a magnetic and pH dually responsive nano-carrier with a multilayer core–shell architecture was prepared from amine-functionalized Fe3O4@SiO2 through the surface-initiated ring opening polymerization of benzyl-L-aspartate N-carboxyanhydride, and then coated with α-methoxy poly(ethylene glycol) (mPEG) via a pH-sensitive benzoic–imine bond. In order to control the layer thickness of poly(benzyl-L-aspartate) (PBLA), a surface passivation agent was applied to modulate the amino density of the functionalized Fe3O4@SiO2 initiator. In this system, the Fe3O4@SiO2 nanoparticles function as a superparamagnetic core used to target the drug loaded nanocarriers to the pathological site. Meanwhile, the mPEG and PBLA segments serve as a pH-sheddable hydrophilic corona and a hydrophobic middle layer used to load the drug via hydrophobic interactions. The obtained materials were characterized by FT-IR, 1H NMR, DLS, zeta-potential, TEM, TGA and hysteresis loop analysis. Furthermore, the loading and release behavior of doxorubicin on the nanocarrier was investigated and it was shown that the drug loaded nanoparticle was relatively stable under physiological conditions and quickly released in response to acidity due to the shedding of mPEG shells through the pH-cleavage of intermediate benzoic–imine bonds. This pH and magnetic responsive nanoparticle has appeared highly promising for the targeted intracellular delivery of hydrophobic chemotherapeutics in cancer therapy.

Imine bond cross-linked poly(ethylene glycol)-block-poly(aspartamide) complex micelle as a carrier to deliver anticancer drugs

Co-reporter:Jingjing Wang, Dongping Zhao, Yinong Wang and Guolin Wu

RSC Advances 2014 vol. 4(Issue 22) pp:11244-11250

Publication Date(Web):08 Jan 2014

DOI:10.1039/C3RA46160B

The aim of this study is to develop degradable core-cross-linked polymeric micelles based on two water soluble methoxy-poly(ethylene glycol)-block-poly(aspartamide) (mPEG-PA) copolymers using the pH-sensitive imine bond. The ring opening polymerization of N-carboxyanhydride (NCA) was utilized to prepare the diblock copolymer methoxy-poly(ethylene glycol)-block-poly(benzyl L-aspartate). Amino and aldehyde modified mPEG-PAs were obtained by aminolysis and oxidation. The mixture of these two mPEG-PA polymer precursors was shown to form reversible core-cross-linked micelles by the formation of an imine linkage without the addition of cross-linker or catalyst. The structure of the prepared polymers was studied using NMR and FT-IR spectroscopy. The pH-sensitivity of the micelles was characterized by DLS. The mPEG-PA cross-linked micelle exhibited good biocompatibility according to the MTT assay against NIH/3T3 cells. The hydrophobic anticancer drug doxorubicin (DOX) was selected as a model drug and loaded into the micelles where it could be quickly released at low pH and was relatively stable under physiological conditions. Thereby, such an excellent nanocarrier provides a favorable platform to construct smart drug delivery systems for cancer therapy.

Magnetic nanoparticles with a pH-sheddable layer for antitumor drug delivery

Co-reporter:Jingjing Wang, Chu Gong, Yinong Wang, Guolin Wu

Colloids and Surfaces B: Biointerfaces 2014 Volume 118() pp:218-225

Publication Date(Web):1 June 2014

DOI:10.1016/j.colsurfb.2014.04.001

A dually responsive nanocarrier with a multilayer core–shell architecture was prepared based on Fe3O4@SiO2 nanoparticles successively coated with poly(benzyl L-aspartate) (PBLA) and poly(ethylene glycol) (PEG) for the purpose of tumor specific drug delivery applications. In this system, PEG chains are connected to the surface via pH-sensitive benzoic-imine bonds and serve as a pH-sheddable hydrophilic corona. Meanwhile, the PBLA segments serve as a hydrophobic middle layer used to load the drugs via hydrophobic interactions. The Fe3O4@SiO2 nanoparticle functions as a superparamagnetic core used to direct the drug loaded nanocarrier to the target pathological site. The obtained materials were characterized with FT-IR, 1H NMR, dynamic light scattering, zeta-potential, TEM, TGA, and hysteresis loop analysis. An anticancer drug doxorubicin (DOX) was selected as the model drug loaded into the nanocarrier, which was relatively stable under physiological conditions due to its neutral hydrophilic shell, and could quickly release the drug in response to increased acidity via shedding of the PEG shells through cleavage of the intermediate benzoic-imine bonds. Meanwhile, the neutral shell shedding would reveal a positively charged nanoparticle surface that is readily taken up by tumor cells. These pH- and magnetic-responsive nanoparticles showed significant potential for use in the targeted intracellular delivery of hydrophobic chemotherapeutics in cancer therapy.

On–off switchable drug release from multi-responsive degradable poly(ether urethane) nanoparticles

Co-reporter:Yangyun Wang, Guolin Wu, Xiaomeng Li, Yinong Wang, Hui Gao and Jianbiao Ma

Biomaterials Science 2013 vol. 1(Issue 6) pp:614-624

Publication Date(Web):08 Mar 2013

DOI:10.1039/C3BM00188A

A novel on–off switchable drug-release system was developed based on a series of multi-responsive degradable poly(ether urethane)s. The multi-segmented poly(ether urethane)s were synthesized through a simple one-pot condensation polymerization of poly(ethylene glycol), 2,2′-dithiodiethanol, N-methyldiethanolamine and hexamethylene diisocyanate. The obtained amphiphilic copolymers could self-assemble into nanoparticles in aqueous solution, which were responsive to temperature, pH and redox potential with tailored phase-transition temperature. The whole process for the responsive behaviours of the poly(ether urethane) nanoparticles was confirmed by light transmission, dynamic light scattering, nuclear magnetic resonance and transmission electron microscopy. The nanoparticles could encapsulate hydrophobic drugs and showed a temperature-triggered accelerated and complete drug-release profile. The mechanism of the temperature-triggered multi-responsive accelerated drug release was also elucidated. These results presented the polymeric nanoparticles as an effective multi-responsive degradable nanocarrier to achieve on–off drug release.

Precise control of drug release from dually responsive poly(ether urethane) nanoparticles

Co-reporter:Yangyun Wang, Xiaomeng Li, Guolin Wu, Jiatong Chen, Yinong Wang, Hui Gao and Jianbiao Ma

RSC Advances 2013 vol. 3(Issue 33) pp:13859-13868

Publication Date(Web):21 May 2013

DOI:10.1039/C3RA41410H

A series of linear poly(ether urethane)s was synthesized based on alternating PEG-diisocyanate of different molecular weight and N-methyldiethanolamine containing ternary amino moieties. The molecular structures of the obtained copolymers were confirmed with nuclear magnetic resonance, Fourier transform infrared spectroscopy and gel permeation chromatography. In aqueous solution, the amphiphilic copolymers could self-assemble into nanoparticles, which showed temperature and pH dual-responsive character. The stimuli-responsive behavior was characterized by light transmission, dynamic light scattering, nuclear magnetic resonance, and transmission electron microscopy. The phase transition temperature (Tp) of the nanoparticles could be modulated by changing the molecular weight of the PEG segments. The encapsulation and release of doxorubicin (DOX) were investigated using the obtained polymeric nanoparticles as carriers. The in vitro experimental results showed that DOX release from the nanoparticles was significantly accelerated when it was conducted at a higher temperature and lower pH value. Importantly, only when the ambient temperature was higher than the corresponding Tp, the drug release could be remarkably enhanced by the pH decrease. The system showed a temperature-triggered pH-dependent drug release. Cell viability and microscopic observation of liver cells (HepG2 cells) treated with the DOX-loaded polymeric nanoparticles demonstrated that the therapeutic activity and the DOX distribution could be precisely controlled by the novel dual-responsive system.

Magnetic and pH-sensitive nanoparticles for antitumor drug delivery

Co-reporter:Shufang Yu, Guolin Wu, Xin Gu, Jingjing Wang, Yinong Wang, Hui Gao, Jianbiao Ma

Colloids and Surfaces B: Biointerfaces 2013 Volume 103() pp:15-22

Publication Date(Web):1 March 2013

DOI:10.1016/j.colsurfb.2012.10.041

A dually responsive nanocarrier with multilayer core–shell architecture was prepared based on Fe3O4@SiO2 nanoparticles coated with mPEG-poly(l-Asparagine). Imidazole groups (pKa ∼ 6.0) were tethered to the side chains of poly(l-Asparagine) segments by aminolysis. These nanoparticles were expected to be sensitive to both magnetic field and pH environment. The obtained materials were characterized with FTIR, dynamic light scattering, ζ-potential, TEM, TGA and hysteresis loop analysis. It was found that this Fe3O4@SiO2–polymer complex can form nano-scale core–shell–corona trilayer particles (∼250 nm) in aqueous solution. The Fe3O4@SiO2, poly(l-Asparagine) and mPEG segments serve as a super-paramagnetic core, a pH-sensitive shell, and a hydrophilic corona, respectively. An antitumor agent, doxorubicin (DOX), was successfully loaded into the nanocarrier via combined actions of hydrophobic interaction and hydrogen bonding. The drug release profiles displayed a pH-dependent behavior. DOX release rate increased significantly as the ambient pH dropped from the physiological pH (7.4) to acidic (5.5). This is most likely due to protonation and a change in hydrophilicity of the imidazole groups in the poly(l-Asparagine) segments. This new approach may serve as a promising platform to formulate magnetic targeted drug delivery systems.Graphical abstractHighlights► Core–shell–corona nanoparticles show sensitivities to both magnetic field and pH environment were developed. ► The Fe3O4@SiO2, poly(l-Asparagine) and mPEG segments serve as a super-paramagnetic core, a pH-sensitive shell, and a hydrophilic corona, respectively. ► DOX was successfully loaded into the nanocarrier via combined actions of hydrophobic interaction and hydrogen bonding. ► The drug release profiles displayed a pH-dependent behavior.

Temperature-triggered redox-degradable poly(ether urethane) nanoparticles for controlled drug delivery

Co-reporter:Yangyun Wang, Guolin Wu, Xiaomeng Li, Jiatong Chen, Yinong Wang and Jianbiao Ma

Journal of Materials Chemistry A 2012 vol. 22(Issue 48) pp:25217-25226

Publication Date(Web):15 Oct 2012

DOI:10.1039/C2JM35186B

A series of biodegradable poly(ether urethane)s that responded to changes in temperature and redox potential was synthesized via a facile one-pot method. The amphiphilic poly(ether urethane)s were comprised of 2,2′-dithiodiethanol, hydrophobic hexamethylene diisocyanate and hydrophilic poly(ethylene glycol) (PEG) segments. The phase transition temperature (Tp) of the prepared poly(ether urethane)s in aqueous solution could be easily controlled by changing the length of the PEG segment or the ratio of PEG to 2,2′-dithiodiethanol and it could be used to trigger the redox-degradable behavior. The redox-responsive disulfide bonds in the polymers could be cleaved in the presence of glutathione (GSH) when the temperature was above Tp, while the degradation was inhibited below Tp. The doxorubicin (DOX)-loaded poly(ether urethane) nanoparticles were prepared in order to investigate their stimuli-responsive release. These nanoparticles also showed a temperature-triggered redox-degradable release profile. Toxicity tests showed that the blank nanoparticles had no toxicity, whereas the DOX-loaded nanoparticles showed high cytotoxicity for liver hepatocellular cells (HepG2). Microscopic observations also revealed that the DOX molecules within the poly(ether urethane) nanoparticles could be released into HepG2 cells in the presence of higher temperature and GSH.

Synthesis of a novel zwitterionic biodegradable poly (α,β-l-aspartic acid) derivative with some l-histidine side-residues and its resistance to non-specific protein adsorption

Co-reporter:Xiaojuan Wang, Guolin Wu, Caicai Lu, Yinong Wang, Yunge Fan, Hui Gao, Jianbiao Ma

Colloids and Surfaces B: Biointerfaces 2011 Volume 86(Issue 1) pp:237-241

Publication Date(Web):1 August 2011

DOI:10.1016/j.colsurfb.2011.04.010

A novel zwitterionic polypeptide derivative, denoted as His-PAsp/PAsp, was successfully synthesized by amidation of Poly (α,β-l-aspartic acid) with l-histidine methyl ester. Turbidity, zeta potential and 1H NMR measurements were used to study the aggregation behaviors of His-PAsp/PAsp under different pH values. The modified polypeptide derivative composed of electro-negatively carboxylic and electro-positively imidazole residues randomly so as to bear opposite charges at pH values above or below the isoelectric point. When the zwitterionic polypeptide was coated on silicon wafer as a model substrate material, the absorption resistance of fibrinogen, a blood protein resulting in the blood coagulation cascade, on the coated surface was measured. It was found that the adsorption amount of fibrinogen on the polypeptide-coated surface depended on the dose of the polypeptide on silicon wafer. Obvious resistance of the fibrinogen adsorption on the polypeptide-coated surface was observed. Since its good biodegradability and superior anti-protein-fouling property, this pH-responsive zwitterionic polypeptide is a promising candidate for surface modification in many biomedical applications, including medical implants, drug delivery carriers, and biosensors.Graphical abstractHighlights► His-PAsp/PAsp zwitterionic polypeptide has been successfully synthesized by a facile way. ► The modified polypeptide derivative had an isoelectric point and bore opposite charges at pH values far high or below the isoelectric point. ► By the surface modification of zwitterionic polypeptide, the surface exhibited resistance to nonspeciﬁc protein adsorption.

A novel delivery system of doxorubicin with high load and pH-responsive release from the nanoparticles of poly (α,β-aspartic acid) derivative

Co-reporter:Xiaojuan Wang, Guolin Wu, Caicai Lu, Weipeng Zhao, Yinong Wang, Yunge Fan, Hui Gao, Jianbiao Ma

European Journal of Pharmaceutical Sciences (30 August 2012) Volume 47(Issue 1) pp:256-264

Publication Date(Web):30 August 2012

DOI:10.1016/j.ejps.2012.04.007

A poly (amino acid)-based amphiphilic copolymer was utilized to fabricate a better micellar drug delivery system (DDS) with improved compatibility and sustained release of doxorubicin (DOX). First, poly (ethylene glycol) monomethyl ether (mPEG) and DOX were conjugated onto polyasparihyazide (PAHy), prepared by hydrazinolysis of the poly (succinimide) (PSI), to afford an amphiphilic polymer [PEG-hyd-P (AHy-hyd-DOX)] with acid-liable hydrazone bonds. The DOX, chemically conjugated to the PAHy, was designed to supply hydrophobic segments. PEGs were also grafted to the polymer via hydrazone bonds to supply hydrophiphilic segments and prolong its lifetime in blood circulation. Free DOX molecules could be entrapped into the nanoparticles fabricated by such an amphiphilic polymer (PEG-hyd-P (AHy-hyd-DOX)), via hydrophobic interaction and π–π stacking between the conjugated and free DOX molecules to obtain a pH responsive drug delivery system with high DOX loaded. The drug loading capacity, drug release behavior, and morphology of the micelles were investigated. The biological activity of micelles was evaluated in vitro. The drug loading capacity was intensively augmented by adjusting the feed ratio, and the maximum loading capacity was as high as 38%. Besides, the DOX-loaded system exhibited pH-dependent drug release profiles in vitro. The cumulative release of DOX was much faster at pH 5.0 than that at pH 7.4. The DOX-loaded system kept highly antitumor activity for a long time, compared with free DOX. This easy-prepared DDS, with features of biocompatibility, biodegradability, high drug loading capacity and pH-responsiveness, was a promising controlled release delivery system for DOX.Download high-res image (129KB)Download full-size image

Temperature-triggered redox-degradable poly(ether urethane) nanoparticles for controlled drug delivery

Co-reporter:Yangyun Wang, Guolin Wu, Xiaomeng Li, Jiatong Chen, Yinong Wang and Jianbiao Ma

Journal of Materials Chemistry A 2012 - vol. 22(Issue 48) pp:NaN25226-25226

Publication Date(Web):2012/10/15

DOI:10.1039/C2JM35186B

On–off switchable drug release from multi-responsive degradable poly(ether urethane) nanoparticles

Co-reporter:Yangyun Wang, Guolin Wu, Xiaomeng Li, Yinong Wang, Hui Gao and Jianbiao Ma

Biomaterials Science (2013-Present) 2013 - vol. 1(Issue 6) pp:NaN624-624

Publication Date(Web):2013/03/08

DOI:10.1039/C3BM00188A