Co-reporter:Bangbang Li, Peng Zhang, Jianwei Du, Xiao Zhao, Youxiang Wang
Colloids and Surfaces B: Biointerfaces 2017 Volume 154(Volume 154) pp:
Publication Date(Web):1 June 2017
DOI:10.1016/j.colsurfb.2017.03.020
•Bioprobes with two morphologies were fabricated by gold nanoparticles.•Thiolated-hyaluronic acid labeled with fluorescence dye was linked to the bioprobes.•HA shell endowed the bioprobes biocompatibility and tumor cells targeted ability.•The rod-shaped bioprobes achieved quickly intracellular fluorescent light-up.•The rod-shaped bioprobes led to excellent photothermal therapy effect.Multifunctional nanoprobe was drawing increased attention in tumor diagnosis and therapy. The simple and effective establishment of the theranostic nanoplatforms was still under urgent need. Meanwhile, the targeting ability and morphology of nanoprobe were essential for the effective endocytosis, which could further affect the diagnosis. In this work, two morphologies of nanoprobes were fabricated using gold nanorods (AuNRs) and gold nanospheres (AuNSs). Thiolated-hyaluronic acid labeled with nile blue (HS-HA-NB), a near-infrared (NIR) fluorescence dye, was coated on the surface of the gold nanoparticles to form stable nanoprobes (AuNR@HS-HA-NB, AuNS@HS-HA-NB). The fluorescence of NB molecules quenched outside cells due to the fluorescence resonance energy transfer (FRET), and recovered after the HA degradation inside the cells. HA also could enhance cellular uptake in CD44 receptor highly expressed human breast carcinoma cells (MCF-7). In this way, bioprobes realized the MCF-7 cell images through intracellular fluorescent light-up. Comparing with the sphere bioprobe, the rod-shaped bioprobe dramatically promoted endocytosis to achieve a better diagnosis effect in a short time. After NIR light irradiation, severe MCF-7 apoptosis was observed with AuNR@HS-HA-NB existed. Our studies suggested that the AuNR@HS-HA-NB nanoparticles were the excellent candidates of versatile bioprobes to realize rapid, precise image and photothermal therapy to MCF-7 cells.Download high-res image (215KB)Download full-size image
Co-reporter:Peng Zhang, Bangbang Li, Jianwei Du, Youxiang Wang
Colloids and Surfaces B: Biointerfaces 2017 Volume 157(Volume 157) pp:
Publication Date(Web):1 September 2017
DOI:10.1016/j.colsurfb.2017.04.056
•BSA-PEI was used to modify gold nanorods and gold nanospheres as gene vector.•The influence of morphology on gene delivery was investigated.•Gold nanoparticles condensed DNA and remained spherical and rod-like morphology.•Rod-like nanoparticles were facilitated to uptake and showed higher transfection.Recent research indicated that the morphology of nanoparticles could result in distinct biological behaviors, thus played an important role in designing efficient gene delivery systems. Among them, gold nanoparticles (AuNPs) with various shapes were widely studied due to the good biocompatibility and easy modification ability. Our recent research indicated that polyethyleneimine-g-bovine serum albumin (BSA-PEI) as non-viral gene vector showed good colloid stability and high transfection efficiency. In this work, BSA-PEI was utilized to modify gold nanospheres (AuNSs) and gold nanorods (AuNRs) to investigate the influence of the morphology on gene delivery. Both AuNS@BSA-PEI and AuNR@BSA-PEI nanoparticles condensed DNA effectively at N/P ratio above 5 and maintained spherical or rod-like morphology respectively. Due to the higher surface charge density at the tips, the rod-like gene complexes were prone to use the tips to contact with cell membrane, which facilitated to be uptaked by HepG2 cells. The endocytosis inhibition experiments showed some differences in the endocytic pathway. Gene transfection experiment showed that the rod-like complexes had almost 100-fold higher of transfection level than that of spherical complexes at the N/P ratio of 20. This work provided a potential strategy for further design of gene vectors with improved transfection results by adjusting the morphology of gene vectors.Spherical and rod-like gene complexes were prepared to investigate the influence of the morphology on gene delivery.Download high-res image (127KB)Download full-size image
Co-reporter:Jianwei Du, Bangbang Li, Peng Zhang, Youxiang Wang
Colloids and Surfaces B: Biointerfaces 2016 Volume 143() pp:37-46
Publication Date(Web):1 July 2016
DOI:10.1016/j.colsurfb.2016.03.023
•Cationized BSA was synthesized and remained α-helical structure to some degree.•cBSA showed specific DNA complexibility and cellular behavior due to the structure.•cBSA/DNA revealed good colloidal stability in physiological salt solution.•cBSA/DNA showed good biocompatibility and effective gene transfection efficiency.In this research, BSA, one of the natural rigid globular proteins with ca. 51% of α-helix secondary structure, was utilized to prepare cationized BSA (cBSA) as gene carrier. Tetraethylenepentamine (TEPA) or polyethylenimine (PEI1800) was grafted to BSA with different grafting levels. Based on the circular dichoism (CD) spectra, all cBSA remained α-helical structure to some degree. This was exciting to endow cBSA with quite different DNA complexibility and cellular biology behavior from the random coiled and flexible polycations such as PEI and poly-l-lysine (PLL). Strangely, the DNA condensability decreased with the increment of TEPA or PEI1800 grafting level. Also, the cBSA could condense DNA effectively to form irregular nanoparticles around 50–200 nm above N/P ratio of 10. On account of the excellent hydration of BSA, the cBSA/DNA complexes revealed good colloidal stability under physiological salt condition. Cell culture experiments indicated this BSA-based gene carrier possessed good cellular compatibility. Surprisingly, cBSA/DNA complexes could be uptaken excellently by up to 90% cells. This might be owing to the agitation effect of α-helical structure and the positive potential of these complexes. BSA-PEI1800/DNA complexes with quick endosome escape even had transfection efficiency as high as PEI25k/DNA complexes. Overall, this paper provided us the potential of cBSA as gene carrier and might have some instructions in the design of protein-based gene delivery system.Cationized BSA was synthesized as gene vectors and remained α-helical structure to some degree, which promoted cell uptake and showed high transfection efficiency.
Co-reporter:Wenyu Li, Yajie Liu, Jianwei Du, Kefeng Ren and Youxiang Wang
Nanoscale 2015 vol. 7(Issue 18) pp:8476-8484
Publication Date(Web):25 Mar 2015
DOI:10.1039/C4NR07037B
Cell-penetrating peptides (CPP) have been widely developed as a strategy to enhance cell penetrating ability and transfection. In this work, octa-arginine modified dextran gene vector with pH-sensitivity was developed via host–guest interactions. α-Cyclodextrin was modified with octa-arginine (CDR), which had excellent cell penetrating ability. Dextran was selected as a backbone and modified with azobenzene as guest units by acid–labile imine bonds (Az-I-Dex). The supramolecular polymer CDR/Az-I-Dex with high a C/A molar ratio (molar ratio of CD on CDR to Az on Az-I-Dex) was unfavorable for DNA condensation. The dextran shell of CDR/Az-I-Dex/DNA polyplexes improved the stability under physiological conditions. However, once treated with acetate buffer (pH 5.4) for 3 h, large aggregates formed rapidly due to the cleavage of the dextran shell. As expected, the vector had cell viability of 80% even when the CDR concentration increased to 100 μg mL−1. Moreover, due to the effective cellular uptake efficiency, CDR/Az-I-Dex/DNA polyplexes had 6–300 times higher transfection efficiency than CDR/DNA polyplexes. It was even higher than high molecular weight PLL-based polyplexes of HEK293 T cells. Importantly, chloroquine as an endosomal escape agent could not improve the transfection of CDR/Az-I-Dex/DNA polyplexes, which indicated that the CDR/Az-I-Dex supramolecular polymer had its own ability for endosomal escape. These results suggested that the CPP-based polyplexes shelled with polysaccharide can be promising non-viral gene delivery carriers.
Co-reporter:Jianwei Du, Ce Tian, Jun Ling, Youxiang Wang
Journal of Controlled Release 2015 Volume 213() pp:e50-e51
Publication Date(Web):10 September 2015
DOI:10.1016/j.jconrel.2015.05.082
Co-reporter:Yunna Kong;Wenyu Li;Qianying Mao
Macromolecular Chemistry and Physics 2015 Volume 216( Issue 14) pp:1507-1515
Publication Date(Web):
DOI:10.1002/macp.201500146
Co-reporter:Jianwei Du, Ce Tian, Yajie Liu, Jun Ling, Youxiang Wang
Colloids and Surfaces B: Biointerfaces 2015 130() pp: 31-39
Publication Date(Web):
DOI:10.1016/j.colsurfb.2015.03.061
Co-reporter:Wenyu Li, Jiale Qu, Jianwei Du, Kefeng Ren, Youxiang Wang, Jingzhi Sun and Qiaoling Hu
Chemical Communications 2014 vol. 50(Issue 67) pp:9584-9587
Publication Date(Web):23 May 2014
DOI:10.1039/C4CC02880E
A novel photoluminescent supramolecular hyperbranched polymer (SHP) without conventional chromophores was constructed for the first time by inclusion complexation between α-cyclodextrin and diethylenetriamine. The SHP showed wide-band fluorescence dependent upon the excitation wavelength.
Co-reporter:Wenyu Li, Jianwei Du, Kun Zheng, Peng Zhang, Qiaoling Hu and Youxiang Wang
Chemical Communications 2014 vol. 50(Issue 13) pp:1579-1581
Publication Date(Web):21 Nov 2013
DOI:10.1039/C3CC48098D
Host–guest assembly provides a universal platform to construct responsive carrier systems for targeted imaging and controllable gene delivery. The best advantage of this strategy is that systems are very easy to handle, do not involve tedious chemical reactions and can be flexibly optimized by changing the functional tags responding to a request.
Co-reporter:San Tang, Zhixiong Huang, Haiwen Zhang, Youxiang Wang, Qiaoling Hu, Hongliang Jiang
Carbohydrate Polymers 2014 Volume 101() pp:104-112
Publication Date(Web):30 January 2014
DOI:10.1016/j.carbpol.2013.09.053
•TMC-g-PCL tightly condensed pDNA despite low molecular weight of TMC.•The uptake of gene complexes was high due to the hydrophobic modification.•The quaternization degree was an important factor for TMC-based gene vector.The ideal gene polyplexes should have a subtle balance between polyplex stability to protect DNA against nucleases, and polyplex instability to permit DNA dissociation inside cells. In this research, low molecular weight trimethylated chitosan was chemically modified with poly(ɛ-caprolactone). Owing to the amphiphilic character, trimethylated chitosan-graft-poly(ɛ-caprolactone) (TMC-g-PCL) formed nanoparticles in aqueous media. TMC-g-PCL nanoparticles could effectively condense pDNA into polyplexes about 200 nm in size. The TMC-g-PCL/DNA polyplexes were stable in physiological salt condition and showed high uptake efficiency probably due to the increasing cell membrane-carrier interaction as a result of hydrophobic modification. However, the high degree of quaternization influenced the buffer capacity of TMC-g-PCL and led to a reduction in the release from the lysosomes. By adding chloroquine to exclude the limitation of lysosome escape, the transfection efficiency of TMC-g-PCL/DNA polyplexes was similar to that of PEI/DNA polyplexes. This study demonstrated the potential of TMC-g-PCL/DNA nanoparticles as an efficient carrier for gene delivery.
Co-reporter:Wenyu Li, Peng Zhang, Kun Zheng, Qiaoling Hu and Youxiang Wang
Journal of Materials Chemistry A 2013 vol. 1(Issue 46) pp:6418-6426
Publication Date(Web):25 Sep 2013
DOI:10.1039/C3TB21241F
Extracellular stability to protect DNA against nucleases and stimulus-triggered intracellular DNA release are key factors in designing non-viral gene vectors. In this study, the diselenide-linked polycation mPEG–SeSe–PEI was developed as a new type of PEG-detachable gene vector for redox-responsive gene delivery. The corresponding stable analog mPEG–PEI and the disulfide-linked polycation mPEG–SS–PEI were synthesized as controls. The results showed that all the PEGylated polycations could condense DNA into tightly packed spherical nanoparticles about 80 nm in size, which showed excellent stability under physiological conditions. The results of zeta-potential measurements, stability tests and DNA release ability assay indicated that at a GSH concentration of 0.3 mM, the diselenide bonds were more easily cleaved than disulfide bonds, which facilitated dePEGylation and DNA release. Meanwhile, it was interestingly found that mPEG–SeSe–PEI/DNA polyplexes showed higher gene expression than mPEG–SS–PEI/DNA polyplexes in both HEK293T and HepG2 cells. Confocal laser scanning microscope (CLSM) images revealed that mPEG–SeSe–PEI/DNA polyplexes showed more efficient endosomal escape ability than mPEG–SS–PEI/DNA polyplexes. Based on these results, the diselenide bonds as a novel strategy are more suitable to address the challenging problem of extracellular stability and intracellular DNA release.
Co-reporter:Lina Chen, Haibo Wang, Yuanfeng Zhang, Youxiang Wang, Qiaoling Hu, Jian Ji
Colloids and Surfaces B: Biointerfaces 2013 Volume 111() pp:297-305
Publication Date(Web):1 November 2013
DOI:10.1016/j.colsurfb.2013.06.021
•Phosphorylcholine modification improved colloid stability and reduced cytotoxicity.•Bioinspired polyplexes were selectively uptaked by liver cancer cells.•Phosphorylcholine-modified polyplexes showed high transfection in cancer cells.We demonstrated here that the phosphorylcholine-modified polyplexes can be explored as effective gene vector for selective uptake and high transfection of cancer cells. 12-acryloyloxy dodecyl phosphorylcholine modified polyethyleneimine (PEI–ADPC) with grafting level about 13%, 8.3% and 4.5% was successfully synthesized. Gel retardation assay indicated that ADPC modification did not affect the DNA condensation ability. The PEI–ADPC13%/DNA and PEI–ADPC8.3%/DNA polyplexes were under 100 nm with a beneficial neutral surface at N/P ratio of 30. Sufficient ADPC shell endowed the polyplexes with high colloidal stability and low cytotoxicity. Compared to PEGylated polyplexes, it was interesting to find out that the PEI–ADPC/DNA polyplexes were selectively uptaked by liver cancer HepG2 cells. At the presence of chloroquine to exclude the limitation of lysosome escape, the ADPC-modified polyplexes showed more effective gene transfection in cancer cells than in normal cells because of the selective cell uptake. In conclusion, the convenient PC-modification modality was found to have both the function of biostability in the physiological environment and targetability toward cancer cells uniquely, which might have great potential use in cancer gene therapy.
Co-reporter:San Tang, Wenyu Li, Ying Zhu, Qiaoling Hu, Youxiang Wang
Colloids and Surfaces A: Physicochemical and Engineering Aspects 2013 Volume 423() pp:124-130
Publication Date(Web):20 April 2013
DOI:10.1016/j.colsurfa.2013.01.028
The biocompatible envelop of virus gives us some inspiration in designing non-viral gene delivery system. In this research, Tat-conjugated hyaluronic acid with different grafting degree was synthesized. By coating HA-Tat to PEI/DNA complexes, the enveloping ternary polyplexes was successfully constructed due to the electrostatic interaction. At N/P/COOH ratio of 8:1:8, spherical nanoparticles were formed with diameter about 150–180 nm. Gel retardation assay indicated the disassembly did not occur. The stability of enveloping polyplexes in physiological condition was improved. HA-Tat envelop improved cell uptake of polyplexes. The intracellular distribution showed the ternary polyplexes could be able to efficiently release DNA and deliver DNA into the nuclei, resulted in higher transfection efficiency than PEI/DNA polyplexes. Thereby, the HA-Tat enveloping polyplexes with facilitated nuclear entry and improved transfection might have a promising application in non-viral gene therapy.Highlights► The stability of HA-Tat enveloping polyplexes was significantly improved. ► HA-Tat envelop improved cell uptake of polyplexes. ► The enveloping polyplexes facilitated nuclear entry and improved transfection.
Co-reporter:Wenyu Li, Youxiang Wang, Lina Chen, Zhixiong Huang, Qiaoling Hu and Jian Ji
Chemical Communications 2012 vol. 48(Issue 81) pp:10126-10128
Publication Date(Web):28 Aug 2012
DOI:10.1039/C2CC34768G
PEG-detachable polyplexes were constructed for the first time via host–guest interactions between β-cyclodextrin and azobenzene. The polyplexes had excellent colloidal stability and competition stability. Moreover, the intracellular light-regulated dePEGylation facilitated DNA release and nuclear entry, thus resulting in efficient transfection.
Co-reporter:Samarendra Maji;Fabian Mitschang;Lina Chen;Qiao Jin;Seema Agarwal
Macromolecular Chemistry and Physics 2012 Volume 213( Issue 16) pp:1643-1654
Publication Date(Web):
DOI:10.1002/macp.201200220
Abstract
In this work, the macromolecular design and modular synthesis of degradable and biocompatible copolymers via radical polymerization and click chemistry is highlighted and the resulting systems are evaluated as gene delivery carriers. Poly(ethylene glycol) (PEG) grafted poly[2-methylene-1,3-dioxepane (MDO)-co-propargyl acrylate (PA)-co-2-(dimethyl aminoethyl methacrylate (DMAEMA)] (MPD) is synthesized using radical polymerization and azide-alkyne click chemistry. The polymers are less cytotoxic and are able to condense plasmid DNA into nanosized particles. The low transfection efficiency of polyplexes in HepG2 cells is significantly improved by mixing Tat peptide with polyplexes.
Co-reporter:Wenyu Li, Lina Chen, Zhixiong Huang, Xiaofei Wu, Yuanfeng Zhang, Qiaoling Hu and Youxiang Wang
Organic & Biomolecular Chemistry 2011 vol. 9(Issue 22) pp:7799-7806
Publication Date(Web):19 Aug 2011
DOI:10.1039/C1OB05886J
Cyclodextrin-modified polycations have been studied widely due to their low cytotoxicity, low immunogenicity and the ability to form inclusion complexes. However, the influence of CD modification on cellular uptake and transfection efficiency of polyplexes is still unclear. In this research, cyclodextrin-modified polyethylenimines (PEI-CD) with different CD-grafting levels were synthesized, which were named PEI-CD15 and PEI-CD41, respectively, according to the CD number per PEI chain. CD modification showed great influence on the DNA condensation ability of the polycation. PEI-CD15 could protect DNA completely above N/P ratio of 2. The particle sizes of these polyplexes were about 120 nm. However, PEI-CD41 could not protect DNA below N/P of 6, and PEI-CD41/DNA polyplexes were larger than 1 μm, even at N/P ratio of 10. Therefore, this research was mainly focused on PEI-CD15. It was interesting that the PEI-CD15/DNA polyplexes at N/P ratio of 8 and 10 displayed excellent stability in physiological salt conditions, probably due to the hydration shell of CDs. The influence of CD modification on the cellular uptake and transfection efficiency of polyplexes depended on the type of the cells. Uptake inhibition experiments indicated that PEI/DNA polyplexes were internalized by HEK293T cells by both clathrin-mediated endocytosis and caveolae-mediated endocytosis. The route of caveolae-mediated endocytosis was significantly promoted after CD modification. So the cell uptake and transfection efficiency of PEI-CD15/DNA polyplexes were significantly improved for HEK293T cells. However, the uptake and transfection efficiency of PEI-CD15/DNA polyplexes in HepG2 cells was similar to that of PEI/DNA polyplexes, probably due to the lack of endogenous caveolins.
Co-reporter:Youxiang Wang, Zhixue Xu, Ran Zhang, Wenyu Li, Lu Yang, Qiaoling Hu
Colloids and Surfaces B: Biointerfaces 2011 Volume 84(Issue 1) pp:259-266
Publication Date(Web):1 May 2011
DOI:10.1016/j.colsurfb.2011.01.007
A facile approach for polymer gene carriers was used to construct hyaluronic acid (HA) shielding polyplexes due to the electrostatic interaction. By adding HA to PEI/DNA complexes, the ξ-potential of ternary polyplexes was changed from positive to negative. Spherical particles with diameter about 250 nm were observed. Ethidium bromide exclusion assay indicated that the electrostatic complexation was loosened after addition of HA. However, DNA disassembly did not occur. The proper reason was that the intensity of negative charges was not strong enough to release DNA from the complexes in our experiment. The stability of PEI/DNA/HA polyplexes in physiological condition was improved and the cytotoxicity was reduced. Comparing with PEI/DNA polyplexes, the uptake and transfection efficiency of HA shielding polyplexes was lower for HEK293T cells probably due to the reduced adsorptive endocytosis, whereas it was higher for HepG2 cells due to HA receptor mediated endocytosis. This facile approach to constructing HA shielding polyplexes might have great potential application in non-viral gene delivery research and tumor therapy.Graphical abstractResearch highlights► Hyaluronic acid (HA) shielding polyplexes was successfully constructed. ► The stability of ternary polyplexes was improved and the cytotoxicity was reduced. ► The uptake and transfection efficiency to HepG2 tumor cells was improved. ► The HA shielding polyplexes might have potential application in tumor gene therapy.
Co-reporter:Yinzhe Li, Youxiang Wang, Dao Wu, Kai Zhang, Qiaoling Hu
Carbohydrate Polymers 2010 Volume 80(Issue 2) pp:408-412
Publication Date(Web):12 April 2010
DOI:10.1016/j.carbpol.2009.11.042
How to construct three-dimensional oriented chitosan scaffolds with improved mechanical property is essential to further design bone-regenerative scaffolds. Materials with multi-layer structures involve excellent mechanical properties. In this research, a facile approach was adopted to construct three-dimensional oriented chitosan scaffolds. The chitosan gel with multi-layer structure was first prepared with in-situ precipitation, and then lyophilization was applied to obtain porous scaffolds. SEM images indicated that the porous scaffolds had spoke-like framework in cross-section and multi-layer structure in vertical-section. Compared with the disordered scaffolds prepared with lyophilization method, the scaffolds prepared with in-situ precipitation method showed a significantly improved compressive strength. With chitosan concentration of 4–5% and drying time of 60 min, the scaffold showed the best comprehensive property with a suitable porosity and a high compressive strength. This novel porous scaffold with three-dimensional oriented structure might have potential application in bone tissue engineering.
Co-reporter:Zhi-xue Xu;Ran Zhang;You-xiang Wang
Journal of Zhejiang University-SCIENCE B 2010 Volume 11( Issue 4) pp:292-297
Publication Date(Web):2010 April
DOI:10.1631/jzus.B0900305
The calcium phosphate (CaP) particles have attracted much attention in gene therapy. How to construct stable gene particles was the determining factor. In this study, hybrid multi-shell CaP gene particles were successfully constructed. First, CaP nanoparticles served as a core and were coated with DNA for colloidal stabilization. The ζ-potential of DNA-coated CaP nanoparticles was −15 mV. Then polyethylenimine (PEI) was added and adsorbed outside of the DNA layer due to the electrostatic attraction. The ζ-potential of hybrid multi-shell CaP particles was slightly positive. With addition of PEI, the hybrid multi-shell particles could condense DNA effectively, which was determined by ethidium bromide (EtBr) exclusion assay. The hybrid particles were spherical and uniform with diameters of about 150 nm at proper conditions. By simple modification of PEI, the hybrid multi-shell CaP gene particles were successfully constructed. They may have great potential in gene therapy.
Co-reporter:Ying Zhu, Youxiang Wang, Qiaoling Hu, Jiacong Shen
Materials Science and Engineering: C 2009 29(3) pp: 1066-1070
Publication Date(Web):
DOI:10.1016/j.msec.2008.08.037
Co-reporter:Youxiang Wang, Ying Zhu, Qiaoling Hu, Jiacong Shen
Acta Biomaterialia 2008 Volume 4(Issue 5) pp:1235-1243
Publication Date(Web):September 2008
DOI:10.1016/j.actbio.2008.04.020
Abstract
Cross-linking of protein macromonomers accompanies the assembly of viral particles, which provides the virus with high stability in the host. Following inspiration, caged polyplexes were fabricated via a biomimetic cross-linker. Thiolated polyethylenimine was synthesized and showed sufficient DNA condensation ability. Spherical particles with a diameter of about 150 nm were formed at an N/P ratio of 10. Shell-cross-linked polyplexes were then constructed by the oxidation of thiol groups in air. All the results indicate that the cross-linking shell via disulfide bonds could improve the stability of polyplexes in the physiological condition and showed a reversible unpacking property at the intracellular GSH concentration. By selecting the proper preparation conditions, polyplexes caged via a biomimetic cross-linker could efficiently release DNA for transfection.
Co-reporter:Xiaolin Li;Jian Ji;Xiaoli Wang;Jiacong Shen
Macromolecular Rapid Communications 2007 Volume 28(Issue 5) pp:660-665
Publication Date(Web):12 MAR 2007
DOI:10.1002/marc.200600723
A novel comb-like derivative CPEG-g-cholesterol was prepared by the reaction of cholesteryl chloroformate with hydroxyl groups of CPEG. The TEM and SEM results showed that CPEG-cholesterol spontaneously aggregated vesicles with the membrane thickness of 4.27 ± 0.48 nm. Compared with the vesicles formed by comb-like PEG (CPEG), the derivation of cholesteryl chloroformate increased the thickness of vesicle membrane and developed corrugations. The hydrophobic doxorubicin (Dox) was added into the solution of CPEG and CPEG-g-cholesterol to test their vesicle stability. The drug-loaded vesicles of CPEG-g-cholesterol still existed but those of CPEG disappeared, which indicated that stability of vesicles was enhanced by the derived cholesteryl chloroformate. The vesicles were further cross-linked by the reaction between divinyl sulfone (DVS) and the hydroxy groups in the side chains of the CPEG and CPEG-g-cholesterol. Both cross-linked vesicles of CPEG and CPEG-g-cholesterol entrapped considerable hydrophobic Dox in the vesicles membrane. The spontaneous vesicles of CPEG-g-cholesterol and the crosslinked vesicles of CPEG and CPEG-g-cholesterol might have great potential as a cargo of the hydrophobic drug.
Co-reporter:Wenyu Li, Jiale Qu, Jianwei Du, Kefeng Ren, Youxiang Wang, Jingzhi Sun and Qiaoling Hu
Chemical Communications 2014 - vol. 50(Issue 67) pp:NaN9587-9587
Publication Date(Web):2014/05/23
DOI:10.1039/C4CC02880E
A novel photoluminescent supramolecular hyperbranched polymer (SHP) without conventional chromophores was constructed for the first time by inclusion complexation between α-cyclodextrin and diethylenetriamine. The SHP showed wide-band fluorescence dependent upon the excitation wavelength.
Co-reporter:Wenyu Li, Youxiang Wang, Lina Chen, Zhixiong Huang, Qiaoling Hu and Jian Ji
Chemical Communications 2012 - vol. 48(Issue 81) pp:NaN10128-10128
Publication Date(Web):2012/08/28
DOI:10.1039/C2CC34768G
PEG-detachable polyplexes were constructed for the first time via host–guest interactions between β-cyclodextrin and azobenzene. The polyplexes had excellent colloidal stability and competition stability. Moreover, the intracellular light-regulated dePEGylation facilitated DNA release and nuclear entry, thus resulting in efficient transfection.
Co-reporter:Wenyu Li, Peng Zhang, Kun Zheng, Qiaoling Hu and Youxiang Wang
Journal of Materials Chemistry A 2013 - vol. 1(Issue 46) pp:NaN6426-6426
Publication Date(Web):2013/09/25
DOI:10.1039/C3TB21241F
Extracellular stability to protect DNA against nucleases and stimulus-triggered intracellular DNA release are key factors in designing non-viral gene vectors. In this study, the diselenide-linked polycation mPEG–SeSe–PEI was developed as a new type of PEG-detachable gene vector for redox-responsive gene delivery. The corresponding stable analog mPEG–PEI and the disulfide-linked polycation mPEG–SS–PEI were synthesized as controls. The results showed that all the PEGylated polycations could condense DNA into tightly packed spherical nanoparticles about 80 nm in size, which showed excellent stability under physiological conditions. The results of zeta-potential measurements, stability tests and DNA release ability assay indicated that at a GSH concentration of 0.3 mM, the diselenide bonds were more easily cleaved than disulfide bonds, which facilitated dePEGylation and DNA release. Meanwhile, it was interestingly found that mPEG–SeSe–PEI/DNA polyplexes showed higher gene expression than mPEG–SS–PEI/DNA polyplexes in both HEK293T and HepG2 cells. Confocal laser scanning microscope (CLSM) images revealed that mPEG–SeSe–PEI/DNA polyplexes showed more efficient endosomal escape ability than mPEG–SS–PEI/DNA polyplexes. Based on these results, the diselenide bonds as a novel strategy are more suitable to address the challenging problem of extracellular stability and intracellular DNA release.
Co-reporter:Wenyu Li, Jianwei Du, Kun Zheng, Peng Zhang, Qiaoling Hu and Youxiang Wang
Chemical Communications 2014 - vol. 50(Issue 13) pp:NaN1581-1581
Publication Date(Web):2013/11/21
DOI:10.1039/C3CC48098D
Host–guest assembly provides a universal platform to construct responsive carrier systems for targeted imaging and controllable gene delivery. The best advantage of this strategy is that systems are very easy to handle, do not involve tedious chemical reactions and can be flexibly optimized by changing the functional tags responding to a request.
Co-reporter:Wenyu Li, Lina Chen, Zhixiong Huang, Xiaofei Wu, Yuanfeng Zhang, Qiaoling Hu and Youxiang Wang
Organic & Biomolecular Chemistry 2011 - vol. 9(Issue 22) pp:NaN7806-7806
Publication Date(Web):2011/08/19
DOI:10.1039/C1OB05886J
Cyclodextrin-modified polycations have been studied widely due to their low cytotoxicity, low immunogenicity and the ability to form inclusion complexes. However, the influence of CD modification on cellular uptake and transfection efficiency of polyplexes is still unclear. In this research, cyclodextrin-modified polyethylenimines (PEI-CD) with different CD-grafting levels were synthesized, which were named PEI-CD15 and PEI-CD41, respectively, according to the CD number per PEI chain. CD modification showed great influence on the DNA condensation ability of the polycation. PEI-CD15 could protect DNA completely above N/P ratio of 2. The particle sizes of these polyplexes were about 120 nm. However, PEI-CD41 could not protect DNA below N/P of 6, and PEI-CD41/DNA polyplexes were larger than 1 μm, even at N/P ratio of 10. Therefore, this research was mainly focused on PEI-CD15. It was interesting that the PEI-CD15/DNA polyplexes at N/P ratio of 8 and 10 displayed excellent stability in physiological salt conditions, probably due to the hydration shell of CDs. The influence of CD modification on the cellular uptake and transfection efficiency of polyplexes depended on the type of the cells. Uptake inhibition experiments indicated that PEI/DNA polyplexes were internalized by HEK293T cells by both clathrin-mediated endocytosis and caveolae-mediated endocytosis. The route of caveolae-mediated endocytosis was significantly promoted after CD modification. So the cell uptake and transfection efficiency of PEI-CD15/DNA polyplexes were significantly improved for HEK293T cells. However, the uptake and transfection efficiency of PEI-CD15/DNA polyplexes in HepG2 cells was similar to that of PEI/DNA polyplexes, probably due to the lack of endogenous caveolins.
.jpg)
![Carbamic acid,N-[2-[(2-aminoethyl)amino]ethyl]-](http://img.cochemist.com/ccimg/36400/36369-40-1.png)
![Carbamic acid,N-[2-[(2-aminoethyl)amino]ethyl]-](http://img.cochemist.com/ccimg/36400/36369-40-1_b.png)
![Ethanaminium,2-[[(dodecyloxy)hydroxyphosphinyl]oxy]-N,N,N-trimethyl-, inner salt](http://img.cochemist.com/ccimg/29600/29557-51-5.png)
![Ethanaminium,2-[[(dodecyloxy)hydroxyphosphinyl]oxy]-N,N,N-trimethyl-, inner salt](http://img.cochemist.com/ccimg/29600/29557-51-5_b.png)
](http://img.cochemist.com/ccimg/27000/26913-06-4.png)
](http://img.cochemist.com/ccimg/27000/26913-06-4_b.png)
