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

Abstract

Antigen uptake by dendritic cells (DCs) is a key step for initiating antigen-specific T cell immunity. In the present study, novel synthetic polymeric nanoparticles were prepared as antigen delivery vehicles to improve the antigen uptake by DCs. Well-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. 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, respectively. Significantly, 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 spectra. In 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 adjuvant. Moreover, as the surface cationic charges of OVA/PEDG nanoparticle formulations reduced, the uptake efficiency decreased correspondingly. Collectively, 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.

Covalent Organic Frameworks: From Materials Design to Biomedical Application

“…Recent decades have witnessed a surge of explorations of biomedical applications in biosensing [ 1 ], bioimaging [ 2 , 3 ], chemotherapy [ 4 , 5 ], gene therapy [ 6 , 7 , 8 , 9 ], immunotherapy [ 10 , 11 ], photodynamic therapy (PDT) [ 12 ], photothermal therapy (PTT) [ 13 , 14 ], tissue engineering [ 15 , 16 ] and others [ 17 ]. Multifarious materials have been widely developed to achieve these objectives, including organic (liposomes [ 18 , 19 , 20 , 21 ], polymer [ 22 , 23 , 24 ], dendrimers [ 25 , 26 ], etc.…”

Designing and Immunomodulating Multiresponsive Nanomaterial for Cancer Theranostics

“…The nano self-assembly formed in an aqueous solution was reported to get activated in the cationic and acidic environment due to the presence of amino moieties causing a disassembled structure. PEDG nanoparticles represented to be an effective delivering agent by increasing the uptake efficiency of antigens by DCs (Li P. et al, 2017).…”

68Ga-labeled amphiphilic polymer nanoparticles for PET imaging of sentinel lymph node metastasis

“…We speculate that with the increase of rigidity of coordination unit, the rotation of ligand molecules is limited, which may improve their chelating stability. Then, different rigid prepolymers were polymerized with polyethylene glycol to obtain amphiphilic alternating copolymers and self-assembled into nanoparticles (NPs) [ 23 ]. Finally, the PET imaging probe was obtained by labeling nanoparticles with 68 Ga and used to explore the potential of lymph node metastasis by PET imaging ( Scheme 1 ).…”