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Self-assembled PEG-b-PDPA-b-PGEM copolymer nanoparticles as protein antigen delivery vehicles to dendritic cells:preparation,characterization and cellular uptake

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Regenerative Biomaterials 2017年第1期4卷 11-20页

作者： Pan Li Junhui Zhou Pingsheng Huang Chuangnian Zhang Weiwei Wang Chen Lia Deling Kong Tianjin Key Laboratory of Biomaterial Research Institute of Biomedical EngineeringChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300192China School of Chemical Engineering and Technology Collaborative Innovation Center of Chemical Science and Engineering(Tianjin)Tianjin UniversityTianjin 300072China

Antigen uptake by dendritic cells(DCs)is a key step for initiating antigen-specific T cell *** the present study,novel synthetic polymeric nanoparticles were prepared as antigen delivery vehicles to improve the antigen uptake by ***-defined cationic and acid-responsive copolymers,monomethoxy poly(ethylene glycol)-block-poly(2-(diisopropyl amino)ethyl methacrylate)-block-poly(2-(guanidyl)ethyl methacrylate)(mPEG-b-PDPA-b-PGEM,PEDG)were synthesized by reversible addition-fragmentation chain transfer polymerization of 2-(diisopropylamino)ethyl methacrylate and N-(tert-butoxycarbonyl)amino ethyl methacrylate monomers,followed by deprotection of tert-butyl protective groups and guanidinylation of obtained primary amines.1H NMR,13C NMR and GPC results indicated the successful synthesis of well-defined PEDG *** copolymers could self-assemble into nanoparticles in aqueous solution,which were of cationic surface charges and showed acid-triggered disassembly contributed by PGEM and PDPA moieties,***,PEDG nanoparticles could effectively condense with negatively charged model antigen ovalbumin(OVA)to form OVA/PEDG nanoparticle formulations with no influence on its secondary and tertiary structures demonstrating by far-UV circular dichroism and UV-vis *** vitro antigen cellular uptake by bone marrow DCs(BMDCs)indicated using PEDG nanoparticles as antigen delivery vehicles could significantly improve the antigen uptake efficiency of OVA compared with free OVA or the commercialized Alum ***,as the surface cationic charges of OVA/PEDG nanoparticle formulations reduced,the uptake efficiency decreased ***,our work suggests that guanidinylated,cationic and acid-responsive PEDG nanoparticles represent a new kind of promising antigen delivery vehicle to DCs and hold great potential to serve as immunoadjuvants in the development of vaccines.

关键词： guanidyl synthetic copolymer nanoparticles antigen delivery dendritic cells

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