用于抗原呈递的生物相容性脂质聚合物阳离子纳米颗粒

Biocompatible Lipid Polymer Cationic Nanoparticles for Antigen Presentation.

作者信息

Pérez-Betancourt Yunys, Távora Bianca de Carvalho Lins Fernandes, Faquim-Mauro Eliana L, Carmona-Ribeiro Ana Maria

机构信息

Biocolloids Laboratory, Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Avenida Professor Lineu Prestes, 748 Butantan, São Paulo CEP 05508-000, Brazil.

Immunopathology Laboratory, Butantan Institute, Av. Vital Brasil, 1500 Butantan, São Paulo 05503-900, Brazil.

出版信息

Polymers (Basel). 2021 Jan 7;13(2):185. doi: 10.3390/polym13020185.

DOI:10.3390/polym13020185

PMID:33430262

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7825723/

Abstract

Biocompatible lipid polymer nanoparticles (NPs) previously used as antimicrobial agents are explored here as immuno-adjuvants. Poly (methyl methacrylate) (PMMA)/dioctadecyldimethylammonium bromide (DODAB)/poly (diallyldimethylammonium chloride) (PDDA) nanoparticles (NPs) were prepared by emulsion polymerization of methyl methacrylate (MMA) in the presence of DODAB and PDDA, with azobisisobutyronitrile (AIBN) as the initiator. NPs characterization after dialysis by dynamic light-scattering yielded 225 ± 2 nm hydrodynamic diameter (Dz), 73 ± 1 mV zeta-potential (), and 0.10 ± 0.01 polydispersity (P). Ovalbumin (OVA) adsorption reduced to 45 ± 2 mV. Balb/c mice immunized with NPs/OVA produced enhanced OVA-specific IgG1 and IgG2a, exhibited moderate delayed type hypersensitivity reaction, and enhanced cytokines production (IL-4, IL-10, IL-2, IFN-γ) by cultured spleen cells. There was no cytotoxicity against cultured macrophages and fibroblasts. Advantages of the PMMA/DODAB/PDDA NPs were high biocompatibility, zeta-potential, colloidal stability, and antigen adsorption. Both humoral and cellular antigen-specific immune responses were obtained.

摘要

此前用作抗菌剂的生物相容性脂质聚合物纳米颗粒（NPs）在此被探索用作免疫佐剂。通过在二甲基二辛基溴化铵（DODAB）和聚二烯丙基二甲基氯化铵（PDDA）存在下，以偶氮二异丁腈（AIBN）为引发剂，对甲基丙烯酸甲酯（MMA）进行乳液聚合制备了聚甲基丙烯酸甲酯（PMMA）/二甲基二辛基溴化铵（DODAB）/聚二烯丙基二甲基氯化铵（PDDA）纳米颗粒（NPs）。透析后通过动态光散射对NPs进行表征，得到流体动力学直径（Dz）为225±2nm，zeta电位（ζ）为73±1mV，多分散性（P）为0.10±0.01。卵清蛋白（OVA）吸附使ζ电位降至45±2mV。用NPs/OVA免疫的Balb/c小鼠产生增强的OVA特异性IgG1和IgG2a，表现出中度迟发型超敏反应，并通过培养的脾细胞增强细胞因子产生（IL-4、IL-10、IL-2、IFN-γ）。对培养的巨噬细胞和成纤维细胞没有细胞毒性。PMMA/DODAB/PDDA NPs的优点是具有高生物相容性、zeta电位、胶体稳定性和抗原吸附性。获得了体液和细胞抗原特异性免疫反应。