Co-reporter:Xiaojin Zhang;Hui Dong;Shuangli Fu;Zhenlin Zhong;Renxi Zhuo
Macromolecular Rapid Communications 2016 Volume 37( Issue 12) pp:993-997
Publication Date(Web):
DOI:10.1002/marc.201600049
Co-reporter:Y.-Z. Wei, R.-X. Zhuo, X.-L. Jiang
Journal of Chromatography A 2016 Volume 1447() pp:122-128
Publication Date(Web):20 May 2016
DOI:10.1016/j.chroma.2016.04.035
•HPLC separation of PEGs and amino-terminated PEGs due to ion-exchange mechanism.•Acetonitrile in water, common silica-based C18 or phenyl RP columns and ELSD used.•No obvious effect of molar mass by isocratic LCCC with optimal volatile buffer.The separation and characterization of polyethylene glycols (PEGs) and amino-substituted derivatives on common silica-based reversed-phase packing columns using isocratic elution is described. This separation is achieved by liquid chromatography under the near critical conditions (LCCC), based on the number of amino functional end groups without obvious effect of molar mass for PEGs. The mobile phase is acetonitrile in water with an optimal ammonium acetate buffer. The separation mechanism of PEG and amino-substituted PEG under the near LCCC on silica-based packing columns is confirmed to be ion-exchange interaction. Under the LCCC of PEG backbone, with fine tune of buffer concentration, the retention factor ratios for benzylamine and phenol in buffered mobile phases, α(benzylamine/phenol)-values, were used to assess the ion-exchange capacity on silica-based reversed-phase packing columns. To the best of our knowledge, this is the first report on separation of amino-functional PEGs independent of the molar mass by isocratic elution using common C18 or phenyl reversed-phase packing columns.
Co-reporter:Xiaojin Zhang;Zhenguo Zhang;Xin Su;Hui Dong;Zhenlin Zhong;Renxi Zhuo
Macromolecular Chemistry and Physics 2015 Volume 216( Issue 16) pp:1712-1717
Publication Date(Web):
DOI:10.1002/macp.201500161
Co-reporter:Ping Liang;Chao-Qun Wang;Hong Chen;Si-Xue Cheng
Polymer International 2015 Volume 64( Issue 5) pp:647-653
Publication Date(Web):
DOI:10.1002/pi.4824
Abstract
A facile strategy for the fabrication of multi-functional polymer/inorganic hybrid nanoparticles for efficient gene and drug co-delivery was developed. A therapeutic gene (p53 plasmid) and a chemotherapy drug (doxorubicin hydrochloride, DOX) were co-loaded simultaneously in hybrid nanoparticles during co-precipitation with high encapsulation efficiency. The prepared heparin–biotin/heparin/CaCO3/calcium phosphate/DNA/DOX (HPB/HP/CaCO3/CaP/DNA/DOX) nanoparticles exhibited pH sensitivity and tumor-targeting property due to the presence of the CaCO3/CaP inorganic component and biotin moiety in the polymer chain, respectively. For comparison, HPB/HP/CaCO3/CaP/DOX hybrid nanoparticles for drug delivery were also fabricated. The cell inhibition effects of different nanoparticles on HeLa cells were evaluated using methylthiazole tetrazolium assay. In vitro study indicated that the gene and drug co-delivery system (HPB/HP/CaCO3/CaP/DNA/DOX) showed a stronger cell growth inhibition effect as compared with the drug delivery system (HPB/HP/CaCO3/CaP/DOX), indicating that HPB/HP/CaCO3/CaP/DNA/DOX hybrid nanoparticles could effectively mediate gene transfection and deliver the drug. The hybrid nanoparticles with good biocompatibility have great promise for gene and drug co-delivery. © 2014 Society of Chemical Industry
Co-reporter:Lian-Sheng Wang;Si-Xue Cheng
Macromolecular Chemistry and Physics 2013 Volume 214( Issue 4) pp:458-463
Publication Date(Web):
DOI:10.1002/macp.201200525
Abstract
Novel random copolymers of 1,4-dioxane-2-one (DON) and 2,2-ethylenedioxy-1,3-propanediol carbonate (EOPDC) are synthesized in bulk at 120 °C using Sn(Oct)2 as a catalyst. The effects of different molar feed ratios of EOPDC/DON on the yield and molecular weight of the copolymers are investigated. The copolymers are obtained with a yield of 55.4–98%. The number-average molecular weight of the copolymer is 0.49–4.18 × 104 g mol−1 with a polydispersity of 1.52–1.68. The poly(DON-co-EOPDC)s obtained are characterized by FTIR, 1H NMR, and 13C NMR spectroscopy, gel-permeation chromatography (GPC), and DSC. The hydrolytic degradation of the copolymer in phosphate buffered saline (PBS) is also investigated. The results show that both the hydrophilicity and the degradation rate of the copolymers increase with increasing copolymer DON content.
Co-reporter:Xiaojin Zhang, Zhenguo Zhang, Xin Su, Mengmeng Cai, Renxi Zhuo, Zhenlin Zhong
Biomaterials 2013 34(38) pp: 10296-10304
Publication Date(Web):
DOI:10.1016/j.biomaterials.2013.09.042
Co-reporter:Xiaojin Zhang;Mengmeng Cai;Zhenlin Zhong;Renxi Zhuo
Macromolecular Rapid Communications 2012 Volume 33( Issue 8) pp:693-697
Publication Date(Web):
DOI:10.1002/marc.201100765
Abstract
A water-soluble polycarbonate with dimethylamino pendant groups, poly(2-dimethylaminotrimethylene carbonate) (PDMATC), is synthesized and characterized. First, the six-membered carbonate monomer, 2-dimethylaminotrimethylene carbonate (DMATC), is prepared via the cyclization reaction of 2-(dimethylamino)propane-1,3-diol with triphosgene in the presence of triethylamine. Although the attempted ring-opening polymerization (ROP) of DMATC with Sn(Oct)2 as a catalyst fails, the ROP of DMATC is successfully carried out with Novozym-435 as a catalyst to give water-soluble aliphatic polycarbonate PDMATC with low cytotoxicity and good degradability.
Co-reporter:Xiaojin Zhang;Zhenguo Zhang;Zhenlin Zhong;Renxi Zhuo
Journal of Polymer Science Part A: Polymer Chemistry 2012 Volume 50( Issue 13) pp:2687-2696
Publication Date(Web):
DOI:10.1002/pola.26051
Abstract
Amphiphilic block-graft copolymers mPEG-b-P(DTC-ADTC-g-Pal) were synthesized by ring-opening polymerization of 2,2-dimethyltrimethylene carbonate (DTC) and 2,2-bis(azidomethyl)trimethylene carbonate (ADTC) with poly(ethylene glycol) monomethyl ether (mPEG) as an initiator, followed by the click reaction of propargyl palmitate and the pendant azido groups on the polymer chains. Stable micelle solutions of the amphiphilic block-graft copolymers could be prepared by adding water to a THF solution of the polymer followed by the removal of the organic solvent by dialysis. Dynamic light scattering measurements showed that the micelles had a narrow size distribution. Transmission electron microscopy images displayed that the micelles were in spherical shape. The grafted structure could enhance the interaction of polymer chains with drug molecules and improve the drug-loading capacity and entrapment efficiency. Further, the amphiphilic block-graft copolymers mPEG-b-P(DTC-ADTC-g-Pal) were low cytotoxic and had more sustained drug release behavior. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012
Co-reporter:Wen-Tao He, Ya-Nan Xue, Na Peng, Wen-Ming Liu, Ren-Xi Zhuo and Shi-Wen Huang
Journal of Materials Chemistry A 2011 vol. 21(Issue 28) pp:10496-10503
Publication Date(Web):07 Jun 2011
DOI:10.1039/C1JM11021G
Organic-inorganic hybrid silica nanoparticles (PM-1, PM-2 and PM-3) with positive surface charge and size below 200 nm were one-pot prepared viaMichael addition between 3-methacryloxypropyl- trimethoxysilane (MPTMS) and polyethylenimine (PEI), followed by hydrolysis and polycondensation of siloxanes. The nanoparticles were characterized by FT-IR, element analysis and particle size analysis. The average sizes of the nanoparticles were 130–180 nm and the surface charge was about 40 mV. The acid–base titration showed that the nanoparticles had higher buffer capacity than PEI 25 kDa. The positively charged nanoparticles can condense negatively charged DNA to form complexes and completely retard the DNA mobility in agarose gel at a weight ratio of 5. The average sizes of PM-1/DNA and PM-2/DNA complexes were below 250 nm and the surface charge of the complexes was in the range of 30–40 mV at the weight ratio of 100. An in vitro transfection assay demonstrated that the transfection efficiencies of the nanoparticles were dependent on the PEI content, and PM-1 showed improved transfection efficiency compared with PEI 25 kDa in the presence of 10% serum. The intracellular trafficking assay of PM-1 nanoparticle/Cy3-labelled DNA complexes in COS-7 cells in the presence of 10% serum indicated that a large amount of complexes crossed the cell membrane and located in the cytoplasm and only a small amount of complexes entered into the cell nucleus after 24 h incubation. The uptake of PM-1 nanoparticle/DNA complexes by COS-7 cells in the presence of serum was higher than that of PEI/DNA complexes. In addition, the cytotoxicity of PM nanoparticles was significantly lower than that of PEI 25 kDa. The results indicate that the synthesized nanoparticles will show potential in nonviral gene delivery.
Co-reporter:Xiaojin Zhang, Zhenlin Zhong, and Renxi Zhuo
Macromolecules 2011 Volume 44(Issue 7) pp:1755-1759
Publication Date(Web):March 2, 2011
DOI:10.1021/ma200137a
Co-reporter:Na Peng, Xi-Ming Xia, Wen-Tao He, Wen-Ming Liu, Shi-Wen Huang, Ren-Xi Zhuo
Polymer 2011 Volume 52(Issue 5) pp:1256-1262
Publication Date(Web):1 March 2011
DOI:10.1016/j.polymer.2011.01.033
Porous films were fabricated from nonporous layer-by-layer multilayers composed of a blend of positively charged disulfide-containing polyamidoamine and poly(allylamine hydrochoride), and negatively charged poly(acrylic acid), followed by removal of cleavable disulfide-containing polycation after incubation in 1 mM DTT solution. The thickness of original multilayered films decreased with the increase of incubation time in DTT solution. Atomic force microscopy (AFM) measurements and electrochemical analysis demonstrated the formation of nanopores with sizes ranging from 50 to 120 nm. The formed porous films were stable in buffer solution at pHs ranging from 7.4 to 1.6, whereas they showed slight changes in pore number and pore size when incubated in PBS buffer at a pH of 10.0. This research might provide a universal method for the fabrication of noncrosslinked porous multilayered films.
Co-reporter:Xiaojin Zhang;Fujie Chen;Zhenlin Zhong;Renxi Zhuo
Macromolecular Rapid Communications 2010 Volume 31( Issue 24) pp:2155-2159
Publication Date(Web):
DOI:10.1002/marc.201000392
Co-reporter:Xiaojin Zhang, Juan Cheng, Qingrong Wang, Zhenlin Zhong and Renxi Zhuo
Macromolecules 2010 Volume 43(Issue 16) pp:6671-6677
Publication Date(Web):July 28, 2010
DOI:10.1021/ma100653u
Amphiphilic miktoarm copolymers mPEG-(hb-PG)-g-PCL bearing one monomethoxy poly(ethylene glycol) (mPEG) chain and several linear poly(ε-caprolactone) (PCL) chains on a hyperbranched polyglycerol (hb-PG) core were designed and synthesized via a combination of anionic polymerization of glycidol and ring-opening polymerization of ε-caprolactone (CL). The polymers were characterized by 1H NMR and gel permeation chromatograph (GPC). The amphiphilic miktoarm copolymers could form stable micelle solutions by adding water to a THF solution of the polymer followed by removal of the organic solvent by dialysis. Dynamic light scattering (DLS) measurements showed that the micelles had a narrow unimodal size distribution. Transmission electron microscopy (TEM) images displayed that the micelles were in regular spherical shape with narrow size distribution. The properties of the copolymers as drug carriers were investigated with prednisone acetate as a model drug. Linear mPEG-b-PCL block copolymers with similar composition were synthesized and used for comparison to investigate the effects of the hyperbranched architecture. The drug loading capacity (DLC) and entrapment efficiency (EE) of amphiphilic hyperbranched miktoarm copolymers mPEG-(hb-PG)-g-PCL were higher than those of amphiphilic linear block copolymers mPEG-b-PCL. Further, the amphiphilic hyperbranched miktoarm copolymers had more sustained drug release behavior.
Co-reporter:Lin Peng, Yuan Gao, Ya-Nan Xue, Shi-Wen Huang, Ren-Xi Zhuo
Biomaterials 2010 31(16) pp: 4467-4476
Publication Date(Web):
DOI:10.1016/j.biomaterials.2010.02.031
Co-reporter:Lei Zhang, Chao-Hua Hu, Si-Xue Cheng, Ren-Xi Zhuo
Colloids and Surfaces B: Biointerfaces 2010 Volume 76(Issue 2) pp:427-433
Publication Date(Web):1 April 2010
DOI:10.1016/j.colsurfb.2009.12.001
Hyperbranched polymers, PG6–PEI25k and PG6–PEI800, were synthesized through grafting branched polyethylenimines (PEIs) with molecular weights of 25 kDa and 800 Da to a polyglycerol core (PG6), respectively. The structure of the polymers was characterized by 1H NMR and FTIR. Through agarose gel electrophoresis retardation assay, PG6–PEI25k and PG6–PEI800 were demonstrated to have capability for DNA binding. PG6–PEI/DNA complexes with different weight ratios were characterized by TEM and particle size analysis. The activity of PG6–PEIs to mediate transfection of reporter plasmids pEGFP-C1 and pGL3-Luc was evaluated on 293T and HeLa cell lines. PG6–PEI25k and PG6–PEI800 showed enhanced levels in transgene expression and decreased cytotoxicities as compared with PEI25k and PEI800, respectively. The results indicated potential applications of PG6–PEIs for efficient gene delivery.
Co-reporter:Lei Zhang, Chao-Hua Hu, Si-Xue Cheng, Ren-Xi Zhuo
Colloids and Surfaces B: Biointerfaces 2010 Volume 79(Issue 2) pp:427-433
Publication Date(Web):1 September 2010
DOI:10.1016/j.colsurfb.2010.05.014
Hyperbranched amphiphilic polymer PG6–PLA–PEG was synthesized through grafting hydrophobic poly(d,l-lactide) (PLA) segments and hydrophilic poly(ethylene glycol) (PEG) blocks to hydrophilic hyperbranched polyglycerol core (PG6), subsequently. To achieve cell targeting property, folic acid (FA) was further incorporated to the hyperbranched polymer to obtain PG6–PLA–PEG–FA. The polymers were characterized by 1H NMR, UV–vis spectroscopy and combined size-exclusion chromatography and multiangle laser light scattering (SEC-MALLS) analysis. Due to the amphiphilicity, PG6–PLA–PEG and PG6–PLA–PEG–FA could self-assemble to form nanoparticles in aqueous solutions. Antineoplastic drug, paclitaxel (PTX), was encapsulated into the nanoparticles. The nanoparticles were observed by transmission electron microscopy (TEM). The targeting property of PG6–PLA–PEG–FA was evaluated in vitro. The results showed that the PTX loaded PG6–PLA–PEG–FA nanoparticles exhibited enhanced inhibition on folate receptor positive tumor cells due to the folate mediated targeting.
Co-reporter:Chao-Hua Hu, Lei Zhang, De-Qun Wu, Si-Xue Cheng, Xian-Zheng Zhang and Ren-Xi Zhuo
Journal of Materials Chemistry A 2009 vol. 19(Issue 20) pp:3189-3197
Publication Date(Web):24 Mar 2009
DOI:10.1039/B817956E
A strategy for efficient gene delivery and expression was developed by encapsulating complexes of plasmid DNA and heparin-modified polyethylenimine into thermosensitive dextran–poly(ε-caprolactone)–2-hydroxylethylmethacrylate–poly(N-isopropylacrylamide) (Dex-PCL-HEMA-PNIPAAm) hydrogels. Thermosensitive hydrogels (THs) with different compositions were prepared and the TH with the highest content of PCL and Dex had the smallest pore size. Branched polyethylenimine (PEI) and heparin (Hep) could spontaneously form Hep/PEI complex particles in aqueous solution with the Hep content ranging from 20–50%. The Hep/PEI complex particles with 20% Hep (HP20), which were spherical in morphology, were well-dispersed and possessed a narrow size distribution with an average diameter of 209 nm. HP20/DNA complexes were then encapsulated in different THs. The release of HP20/DNA complexes from the hydrogels occurred mainly within the first 72 h in phosphate-buffered saline. HP20/DNA complexes used to transfect HeLa and 293T cells yielded luciferase expression levels which were 50–140-fold higher in serum-containing media, compared with PEI/DNA complexes in serum-free media. HP20/DNA complexes encapsulated in Dex-PCL-HEMA-PNIPAAm hydrogels not only exhibited appreciable transfection efficiency, but also provided a prolonged transgene expression, indicating that the combination of heparin-modified PEI and thermosensitive hydrogels has great potential for localized gene delivery.
Co-reporter:Chao-Hua Hu, Xian-Zheng Zhang, Lei Zhang, Xiao-Ding Xu and Ren-Xi Zhuo
Journal of Materials Chemistry A 2009 vol. 19(Issue 47) pp:8982-8989
Publication Date(Web):23 Oct 2009
DOI:10.1039/B916310G
Temperature- and pH-sensitive poly(N-isopropylacrylamide-co-acrylic acid-co-poly(ε-caprolactone)) (P(NIPAAm-co-AAc-co-PCL)) hydrogels were synthesized to immobilize plasmid DNA (pDNA) compacted with heparin-modified polyethyleneimine (Hep/PEI). The interior morphology of the prepared hydrogels observed by SEM showed macroporous structure clearly. It was found that the swollen hydrogels with low PCL content were able to immobilize efficiently plasmid DNA complexes. The de-swollen hydrogels resulted in a sustained release of the immobilized DNA complexes, and the released DNA complexes exhibited considerable gene expression activity with reduced cytotoxicity as compared with DNA complexes in the solution, indicating that the heparin-modified PEI/DNA-complex-immobilized environment-sensitive hydrogel has promising applications in substrate-mediated gene delivery.
Co-reporter:De-Qun Wu, Fen Qiu, Tao Wang, Xue-Jun Jiang, Xian-Zheng Zhang and Ren-Xi Zhuo
ACS Applied Materials & Interfaces 2009 Volume 1(Issue 2) pp:319
Publication Date(Web):December 1, 2008
DOI:10.1021/am8000456
A series of hydrogels containing a biodegradable dextran (Dex) chain grafted with a hydrophobic poly(ϵ-caprolactone)−2-hydroxylethyl methacrylate (PCL−HEMA) chain and a thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) chain were synthesized. The molecular weight of PCL−HEMA was determined by gel permeation chromatography, and the inner morphology of the hydrogel was observed by scanning electron microscopy. The release profiles from the hydrogels were investigated using bovine serum albumen as a model drug. It was found that the release behavior could be adjusted by varying the composition of the hydrogel. In vitro cytotoxicity studies of the hydrogels showed that the copolymer Dex−PCL−HEMA/PNIPAAm exhibited low cytotoxicity. The in vivo degradation and histological studies demonstrated that the hydrogels had good biocompatibility and were promising for use as an injectable polymeric scaffold for tissue engineering applications.Keywords: biocompatibility; histology study; injectable biodegradable hydrogel; thermoresponsive
Co-reporter:Bo Lu, Yun-Xia Sun, Yun-Qiu Li, Xian-Zheng Zhang and Ren-Xi Zhuo
Molecular BioSystems 2009 vol. 5(Issue 6) pp:629-637
Publication Date(Web):17 Apr 2009
DOI:10.1039/B822505B
Low transfection efficiency and inactivation by serum are the major drawbacks for cationic polymers when used as non-viral gene vectors. Here, a series of N-succinyl-chitosan-graft-polyethylenimine (NSC-g-PEI) copolymers with different compositions were synthesized through grafting low molecular weight PEI (800 Da) to N-succinyl-chitosan. An agarose gel electrophoresisassay showed NSC-g-PEIs had good binding capability with DNA and the particle size of the NSC-g-PEI–DNA complexes was between 150 to 300 nm as determined by a Zeta sizer. In vitro transfection of NSC-g-PEI–DNA complexes for 293T, HeLa and CHO cells was investigated. It was found that the transfection efficiency of NSC-g-PEI–DNA complexes was higher than that of DNA combined PEI (25 kDa) and the transfection efficiency increased with the increasing GD of PEI. More importantly, the NSC-g-PEI–DNA complexes were stable and the transfection efficiency was not affected obviously in the presence of serum with different concentrations. In addition, NSC-g-PEIs had a lower cytotoxicity than PEI (25 kDa) and the toxicity increased with increasing GD of PEI. The NSC-g-PEI copolymers will have a good potential as efficient non-viral gene vectors in the presence of serum.
Co-reporter:Xuan Zeng;Yun-Xia Sun;Xian-Zheng Zhang;Si-Xue Cheng
Pharmaceutical Research 2009 Volume 26( Issue 8) pp:1931-1941
Publication Date(Web):2009 August
DOI:10.1007/s11095-009-9920-4
To improve the gene delivery efficiency and safety of non-viral vector in liver cells, avidin, which exhibited good biocompatibility and remarkable accumulation in liver, was bioconjugated with biotinylated polyethylenimine to obtain a novel gene vector.Biotinylated polyethyleneimine/avidin bioconjugate (ABP) was synthesized through grafting biotin to high molecular weight branched polyethylenimine (PEI, 25 kDa) and then bioconjugating with avidin by the biotin-avidin interaction. Physiochemical characteristics of ABP/pDNA complexes were analyzed, and in vitro cytotoxicity and transfection of ABP were also evaluated in HepG2, Hela and 293 T cells by using 25 kDa PEI as the control.It was found that ABP was able to condense pDNA efficiently at N/P ratio of 4. The particle sizes of ABP/pDNA complexes were less than 220 nm, and the average surface charges were around 27 mV at the N/P ratio ranging from 2 to 60. Among three different cell lines, ABP and its DNA complexes demonstrated much lower cytotoxicity and higher transfection efficacy in HepG2 cells as compared with 25 kDa PEI.ABP presented higher transfection efficacy and safety in HepG2 cells due to the biocompatibility of avidin and the specific interactions between avidin and HepG2 cells.
Co-reporter:Qiao Zhang;Dong Zhao;Xian-Zheng Zhang;Si-Xue Cheng
Journal of Biomedical Materials Research Part B: Applied Biomaterials 2009 Volume 91B( Issue 1) pp:172-180
Publication Date(Web):
DOI:10.1002/jbm.b.31387
Abstract
Calcium-phosphate/deoxyribose nucleic acid (Ca-P/DNA) co-precipitates were deposited on or encapsulated in fast-degrading polymer films with surface erosion degradation mechanism to mediate cell transfection. The polymer, cholic acid functionalized star poly(DL-lactide), was synthesized through the ring-opening polymerization of DL-lactide initiated by cholic acid. The releases of DNA from the Ca-P/DNA co-precipitates deposited film and the Ca-P/DNA co-precipitates encapsulated film were determined and compared. The in vitro gene transfections of HEK293 cells, Hela cells, and NIH 3T3 cells showed that the expression of pGL3-Luc plasmid could be effectively mediated by the Ca-P/DNA co-precipitates deposited and encapsulated polymer films. In addition, the films did not exhibit any additional cytotoxicity to the cells during the transfections, indicating that the fast-degrading polymer films have great potential in localized gene delivery. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Co-reporter:Hua Wei, Cui-yun Yu, Cong Chang, Chang-yun Quan, Shao-bo Mo, Si-xue Cheng, Xian-zheng Zhang and Ren-xi Zhuo
Chemical Communications 2008 (Issue 38) pp:4598-4600
Publication Date(Web):01 Aug 2008
DOI:10.1039/B811553B
An interesting transition from spherical micelles to vesicles, which was time and temperature dependent, was observed for the first time; it is tentatively attributed to the thermal hysteresis of temperature-responsive poly(N-isopropylacrylamide).
Co-reporter:Yun-Xia Sun, Wang Xiao, Si-Xue Cheng, Xian-Zheng Zhang, Ren-Xi Zhuo
Journal of Controlled Release 2008 Volume 128(Issue 2) pp:171-178
Publication Date(Web):4 June 2008
DOI:10.1016/j.jconrel.2008.03.004
Gene vectors, (dextran-hexamethylenediisocyanate)-g-polyethylenimines ((Dex-HMDI)-g-PEIs), were synthesized through grafting low molecular weight (800 Da) branched polyethylenimine (PEI) to HMDI functionalized dextrans with two different molecular weights. The buffer capabilities of (Dex-HMDI)-g-PEIs were examined by acid–base titration. The titration profiles show that both (Dex-HMDI)-g-PEIs have the similar buffer capability regardless of the different molecular weight of dextran. Physiochemical characteristics of (Dex-HMDI)-g-PEI/DNA complexes were analyzed by agarose gel electrophoresis, and particle size and ζ-potential measurements. The result of gel electrophoresis suggests that both (Dex-HMDI)-g-PEIs are able to condense DNA efficiently at N/P ratios higher than 4. The particle sizes of (Dex-HMDI)-g-PEI/DNA complexes are around 160–250 nm, and the surface charges are around 19–23 mV at the N/P ratios ranging from 10 to 60. The morphology of complexes was observed by scanning electron microscopy (SEM) and the images show that nano-sized complexes display a regular spherical shape. In vitro cell viability and transfection were evaluated in 293T and HeLa cells using 25 kDa PEI as a control. The cytotoxicity of (Dex-HMDI)-g-PEIs is lower than that of 25 kDa PEI. The gene transfection efficiency of (Dex-HMDI)-g-PEI/DNA complexes at certain N/P ratios in 293T cells is higher than or comparable to 25 kDa PEI/DNA complex at its optimal N/P ratio of 10. In addition, comparing with (Dex-HMDI)-g-PEI with a high molecular weight dextran, (Dex-HMDI)-g-PEI with a low molecular weight dextran demonstrates lower cytotoxicity and higher transfection efficiency.
Co-reporter:Gwang-Chol Kim, Yong-Yong Li, Yan-Feng Chu, Si-Xue Cheng, Ren-Xi Zhuo, Xian-Zheng Zhang
European Polymer Journal 2008 Volume 44(Issue 9) pp:2761-2767
Publication Date(Web):September 2008
DOI:10.1016/j.eurpolymj.2008.07.015
This paper demonstrated the preparation of temperature-responsive magnetomicelles that consist of a functionalized hexagonal magnetic core, Fe3O4-undecylenic acid (Fe3O4-UA), and an amphiphilic surface layer of temperature-responsive polymer. The functionalized magnetic Fe3O4-UA core was prepared by a suspension-oxidation reaction in an aqueous solution, during which the formation of the Fe3O4 and coordination of UA to the Fe3O4 occurred simultaneously. Amphiphilic poly(undecylenic acid-co-N-isopropylacrylamide) (P(UA-co-NIPAAm)) was grafted to the Fe3O4-UA core as a temperature-responsive micellar surface layer to prepare well dispersed Fe3O4-UA-g-P(UA-co-NIPAAm) magnetomicelles with the size of around 8 nm in water. The application of resulted nanosized Fe3O4-UA-g-P(UA-co-NIPAAm) magnetomicelles in controlled drug delivery was further investigated and it was found that resulting magnetomicelles exhibited good potential for temperature triggered controlled drug release.
Co-reporter:Hua Wei ; De-Qun Wu ; Qian Li ; Cong Chang ; Jin-Ping Zhou ; Xian-Zheng Zhang
The Journal of Physical Chemistry C 2008 Volume 112(Issue 39) pp:15329-15334
Publication Date(Web):September 9, 2008
DOI:10.1021/jp8056527
A novel amphiphilic block copolymer poly(N-isopropylacrylamide-co-N-hydroxymethylacrylamide-co-3-(trimethoxysilyl)propyl methacrylate)-b-poly(ε-caprolactone) (P(NIPAAm-co-HMAAm-co-MPMA)-b-PCL) bearing thermosensitivity as well as biodegradability was synthesized for the production of hollow spheres. A three-step approach was employed to prepare shell cross-linked (SCL), thermoresponsive hybrid hollow spheres: (1) micellization of P(NIPAAm-co-HMAAm-co-MPMA)-b-PCL, (2) cross-linking of the hydrophilic shell via acid-catalyzed sol−gel process, and then (3) degrading the PCL core with an enzyme. Transmission electron microscopy (TEM) studies and size measurements showed that the resultant hollow spheres exhibited regularly globular shape with diameter of around 170 nm. The structures of the SCL micelles and the hollow spheres were characterized by Fourier-transform infrared (FT-IR) measurements and laser light scattering (LLS) analyses. The SCL hollow spheres showed reversible dispersion/aggregation in response to temperature cycles through lower critical solution temperature (LCST) of the outer cross-linked shell at around 37 °C. The SCL micelles as well as hollow spheres prepared here may be used as nanocarriers for catalytic particles, molecules with electronic and photonic functions, as well as biological and medical species.
Co-reporter:Bo Lu, Xiao-Ding Xu, Xian-Zheng Zhang, Si-Xue Cheng and Ren-Xi Zhuo
Biomacromolecules 2008 Volume 9(Issue 10) pp:
Publication Date(Web):August 13, 2008
DOI:10.1021/bm8004676
To develop chitosan-based efficient gene vectors, chitosans with different molecular weights were chemically modified with low molecular weight polyethylenimine. The molecular weight and composition of polyethylenimine grafted N-maleated chitosan (NMC-g-PEI) copolymers were characterized using gel permeation chromatography (GPC) and 1H NMR, respectively. Agarose gel electrophoresis assay showed that NMC-g-PEI had good binding ability with DNA, and the particle size of the NMC-g-PEI/DNA complexes was 200−400 nm, as determined by a Zeta sizer. The nanosized complexes observed by scanning electron microscopy (SEM) exhibited a compact and spherical morphology. The NMC-g-PEI copolymers showed low cytotoxicity and good transfection activity, comparable to PEI (25 KDa) in both 293T and HeLa cell lines, except for NMC50K-g-PEI. The results indicated that the molecular weight of NMC-g-PEI has an important effect on cytotoxicity and transfection activity, and low molecular weight NMC-g-PEI has a good potential as efficient nonviral gene vectors.
Co-reporter:Wei Li
Journal of Polymer Science Part A: Polymer Chemistry 2003 Volume 41(Issue 1) pp:152-159
Publication Date(Web):25 NOV 2002
DOI:10.1002/pola.10570
Macroporous, temperature-sensitive poly(N-isopropylacrylamide) (PNIPAAm) hydrogels were synthesized with poly(ethylene glycol)s (PEGs; molecular weight = 2000–6000) as the pore-forming agents. The influence of the molecular weight and PEG content on the responsive kinetics of these macroporous hydrogels was investigated. The PEG-modified PNIPAAm hydrogels were characterized by the swelling ratio, deswelling–reswelling kinetics, Fourier transform infrared, and differential scanning calorimetry. The morphology of these hydrogels was analyzed with scanning electron microscopy. The prepared macroporous hydrogels exhibited some unique properties in comparison with the gels with low molecular weight PEGs (molecular weight < 2000) as the pore-forming agents. In addition, a preliminary study on the controlled release of bovine serum albumin from these macroporous hydrogels was carried out. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 152–159, 2003
Co-reporter:J.-T. Zhang;S.-X. Cheng;R.-X. Zhuo
Journal of Polymer Science Part A: Polymer Chemistry 2003 Volume 41(Issue 15) pp:2390-2392
Publication Date(Web):16 JUN 2003
DOI:10.1002/pola.10785
Macroporous poly(N-isopropylacrylamide) (PNIPA) hydrogels with improved temperature sensitivity were prepared in aqueous glucose solutions. Compared with the conventional PNIPA hydrogel prepared in water, the gels thus prepared showed significantly faster response as the temperature increased above the lower critical solution temperature. The improved properties were due to the macroporous structure, that was formed during gel preparation caused by the phase separation in glucose solutions.
Co-reporter:Guo-Ping Yan;Mian-Yi Xu;Xu Zhang;Li-Yun Li;Mai-Li Liu;Chao-Hui Ye
Polymer International 2002 Volume 51(Issue 10) pp:
Publication Date(Web):30 OCT 2002
DOI:10.1002/pi.922
Water-soluble polyester ligands were synthesized by the polycondensation of diethylenetriaminepentaacetic dianhydride (DTPAA) with protected polyalcohol 3-O-benzyl-glycerol (3-O-Bz-GLYC), pentaerythritol monobenzaldehyde (S-Bz-PETO) and N-benzyldiethanolamine (N-Bz-DEA), respectively, and the protecting groups were then removed by hydrogenation to give polyesters P(DTPA–GLYC), P(DTPA–PETO) and P(DTPA–DEA). In the same manner, by adding ethylene glycol (EG) monomer into the polymerization system, polyesters P(DTPA–GLYC–EG), P(DTPA–PETO–EG) and P(DTPA–DEA–EG) were also synthesized. Pyridoxamine was chosen as a liver-targeting group and it was first chlorocarbonylated and then incorporated into polyesters. The polyester ligands containing pyridoxamine group thus prepared were further reacted with GdCl3 in water at room temperature to give the corresponding hepatic-targeting polyester gadolinium complexes. These macromolecular ligands and their gadolinium complexes were characterized by 1H NMR, IR, UV and elementary analysis. Relaxivity studies showed that these polyester gadolinium complexes possess higher relaxation effectiveness than that of the clinically used small molecular gadolinium complex Gd-DTPA. In vitro cytotoxicity assay demonstrated that these macromolecular ligands and their gadolinium complexes have low cytotoxicity to the human normal liver cells (L-02). Magnetic resonance imaging of the liver in rats indicated that these polyester MRI contrast agents containing pyridoxamine group exhibit liver-targeting property.
© 2002 Society of Chemical Industry
Co-reporter:Zongyun Chen, Song Han, Zhijian Cao, Yingliang Wu, Renxi Zhuo, Wenxin Li
Peptides (January 2013) Volume 39() pp:145-151
Publication Date(Web):1 January 2013
DOI:10.1016/j.peptides.2012.11.013
Animal toxins are powerful tools for testing the pharmacological, physiological, and structural characteristics of ion channels, proteases, and other receptors. However, most animal toxins are disulfide-rich peptides that are difficult to produce functionally. Here, a glutathione S-transferase (GST) fusion expression strategy was used to produce four recombinant animal toxin peptides, ChTX, StKTx23, BmP01, and ImKTx1, with different isoelectric points from 4.7 to 9.2. GST tags were removed by enterokinase, a widely used and effective commercial protease that cleaves after lysine at the cleavage site DDDDK. Using this strategy, two disulfide-rich animal toxins ChTX and StKTx23 were obtained successfully with a yield of approximately 1–2 mg/l culture. Electrophysiological experiments further showed that these two recombinant toxins showed good bioactivities, indicating that our method was effective in producing large amounts of functional disulfide-rich animal toxins. Interestingly, by analyzing the separated fractions of BmP01, StKTx23, and ImKTx1 using matrix-assisted laser desorption ionization time-of-flight mass spectrometry, four new enterokinase secondary cleavage sites were found, consisting of the sequences “WEYR,” “EDK,” “QNAR,” and “DNDK.” To our knowledge, this is the first report of the presence of secondary cleavage sites for commercial enterokinase in animal toxins. These findings will help us use commercial enterokinase appropriately as a cleavage tool in the production of animal toxins.Highlights► A glutathione S-transferase (GST) fusion expression strategy was used to produce four animal toxins. ► GST tags were removed by enterokinase that cleaves after lysine at the cleavage site DDDDK. ► Four enterokinase secondary cleavage sites “WEYR”, “EDK”, “QNAR”, and “DNDK” were found. ► It is the first report of the presence of secondary cleavage sites for commercial enterokinase in animal toxins.
Co-reporter:Hua Wei, Cui-yun Yu, Cong Chang, Chang-yun Quan, Shao-bo Mo, Si-xue Cheng, Xian-zheng Zhang and Ren-xi Zhuo
Chemical Communications 2008(Issue 38) pp:NaN4600-4600
Publication Date(Web):2008/08/01
DOI:10.1039/B811553B
An interesting transition from spherical micelles to vesicles, which was time and temperature dependent, was observed for the first time; it is tentatively attributed to the thermal hysteresis of temperature-responsive poly(N-isopropylacrylamide).
Co-reporter:Chao-Hua Hu, Xian-Zheng Zhang, Lei Zhang, Xiao-Ding Xu and Ren-Xi Zhuo
Journal of Materials Chemistry A 2009 - vol. 19(Issue 47) pp:NaN8989-8989
Publication Date(Web):2009/10/23
DOI:10.1039/B916310G
Temperature- and pH-sensitive poly(N-isopropylacrylamide-co-acrylic acid-co-poly(ε-caprolactone)) (P(NIPAAm-co-AAc-co-PCL)) hydrogels were synthesized to immobilize plasmid DNA (pDNA) compacted with heparin-modified polyethyleneimine (Hep/PEI). The interior morphology of the prepared hydrogels observed by SEM showed macroporous structure clearly. It was found that the swollen hydrogels with low PCL content were able to immobilize efficiently plasmid DNA complexes. The de-swollen hydrogels resulted in a sustained release of the immobilized DNA complexes, and the released DNA complexes exhibited considerable gene expression activity with reduced cytotoxicity as compared with DNA complexes in the solution, indicating that the heparin-modified PEI/DNA-complex-immobilized environment-sensitive hydrogel has promising applications in substrate-mediated gene delivery.
Co-reporter:Chao-Hua Hu, Lei Zhang, De-Qun Wu, Si-Xue Cheng, Xian-Zheng Zhang and Ren-Xi Zhuo
Journal of Materials Chemistry A 2009 - vol. 19(Issue 20) pp:NaN3197-3197
Publication Date(Web):2009/03/24
DOI:10.1039/B817956E
A strategy for efficient gene delivery and expression was developed by encapsulating complexes of plasmid DNA and heparin-modified polyethylenimine into thermosensitive dextran–poly(ε-caprolactone)–2-hydroxylethylmethacrylate–poly(N-isopropylacrylamide) (Dex-PCL-HEMA-PNIPAAm) hydrogels. Thermosensitive hydrogels (THs) with different compositions were prepared and the TH with the highest content of PCL and Dex had the smallest pore size. Branched polyethylenimine (PEI) and heparin (Hep) could spontaneously form Hep/PEI complex particles in aqueous solution with the Hep content ranging from 20–50%. The Hep/PEI complex particles with 20% Hep (HP20), which were spherical in morphology, were well-dispersed and possessed a narrow size distribution with an average diameter of 209 nm. HP20/DNA complexes were then encapsulated in different THs. The release of HP20/DNA complexes from the hydrogels occurred mainly within the first 72 h in phosphate-buffered saline. HP20/DNA complexes used to transfect HeLa and 293T cells yielded luciferase expression levels which were 50–140-fold higher in serum-containing media, compared with PEI/DNA complexes in serum-free media. HP20/DNA complexes encapsulated in Dex-PCL-HEMA-PNIPAAm hydrogels not only exhibited appreciable transfection efficiency, but also provided a prolonged transgene expression, indicating that the combination of heparin-modified PEI and thermosensitive hydrogels has great potential for localized gene delivery.
Co-reporter:Wen-Tao He, Ya-Nan Xue, Na Peng, Wen-Ming Liu, Ren-Xi Zhuo and Shi-Wen Huang
Journal of Materials Chemistry A 2011 - vol. 21(Issue 28) pp:NaN10503-10503
Publication Date(Web):2011/06/07
DOI:10.1039/C1JM11021G
Organic-inorganic hybrid silica nanoparticles (PM-1, PM-2 and PM-3) with positive surface charge and size below 200 nm were one-pot prepared viaMichael addition between 3-methacryloxypropyl- trimethoxysilane (MPTMS) and polyethylenimine (PEI), followed by hydrolysis and polycondensation of siloxanes. The nanoparticles were characterized by FT-IR, element analysis and particle size analysis. The average sizes of the nanoparticles were 130–180 nm and the surface charge was about 40 mV. The acid–base titration showed that the nanoparticles had higher buffer capacity than PEI 25 kDa. The positively charged nanoparticles can condense negatively charged DNA to form complexes and completely retard the DNA mobility in agarose gel at a weight ratio of 5. The average sizes of PM-1/DNA and PM-2/DNA complexes were below 250 nm and the surface charge of the complexes was in the range of 30–40 mV at the weight ratio of 100. An in vitro transfection assay demonstrated that the transfection efficiencies of the nanoparticles were dependent on the PEI content, and PM-1 showed improved transfection efficiency compared with PEI 25 kDa in the presence of 10% serum. The intracellular trafficking assay of PM-1 nanoparticle/Cy3-labelled DNA complexes in COS-7 cells in the presence of 10% serum indicated that a large amount of complexes crossed the cell membrane and located in the cytoplasm and only a small amount of complexes entered into the cell nucleus after 24 h incubation. The uptake of PM-1 nanoparticle/DNA complexes by COS-7 cells in the presence of serum was higher than that of PEI/DNA complexes. In addition, the cytotoxicity of PM nanoparticles was significantly lower than that of PEI 25 kDa. The results indicate that the synthesized nanoparticles will show potential in nonviral gene delivery.
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