Vaccine adjuvant platform and fluorescence imaging of amphiphilic γ-PGA-IMQ-LA-FL conjugates

被引：3

作者：

Yin, Wenzhu ^{[1
,2
,3
]}

Xuan, Dechun ^{[4
]}

Deng, Bihua ^{[1
,2
]}

Zhou, Mingxu ^{[1
,2
]}

Ma, Fang ^{[1
,2
]}

Zhang, Jinqiu ^{[1
,2
,4
]}

Lu, Yu ^{[1
,2
,3
,4
]}

机构：

[1] Jiangsu Acad Agr Sci, Natl Res Ctr Engn & Technol Vet Biolog, Inst Vet Immunol & Engn, Jiangsu Key Lab Food Qual, Nanjing 210014, Peoples R China

[2] Jiangsu Acad Agr Sci, Safety State Key Lab Cultivat Base, Minist Sci & Technol, Nanjing 210014, Peoples R China

[3] Jiangsu Coinnovat Ctr Prevent & Control Important, Yangzhou 225009, Jiangsu, Peoples R China

[4] Jiangsu Univ, Sch Pharm, Zhenjiang 212013, Jiangsu, Peoples R China

来源：

MATERIALS ADVANCES | 2022年 / 3卷 / 05期

基金：

中国国家自然科学基金;

关键词：

MACROPHAGE POLARIZATION; ADAPTIVE IMMUNITY; DENDRITIC CELLS; GLUTAMIC ACID; INNATE IMMUNE; NANOPARTICLES; PACLITAXEL; DELIVERY; AGONISTS;

D O I：

10.1039/d1ma01169c

中图分类号：

T [工业技术];

学科分类号：

08 ;

摘要：

Adjuvants have proven to be integral components in most vaccines for promoting appropriate immune responses at both innate and adaptive levels. Imiquimod (IMQ, R837), an agonist for Toll-like receptors 7 (TLR7), is a potent molecular activator of the innate immune system and has been developed as an adjuvant for immunotherapy. However, due to its pharmacokinetic profile, IMQ may induce strong local and systemic inflammatory reactions and is poorly tolerated. To overcome these hurdles, herein, we conjugate IMQ and lauryl alcohol (LA) to the backbone of biodegradable poly (gamma-glutamic acid) (gamma-PGA) to prepare an amphiphilic polymer (shortened to gamma-PGA-IMQ-LA) with improved stability and biodistribution of IMQ. In order to investigate the distribution of the amphiphilic polymer in vitro and in vivo, fluorescein was grafted to the lateral chain to synthesize fluorescent-labeled gamma-PGA-IMQ-LA-FL (shortened to FIP). The novel amphiphilic FIP polymer was characterized via(1)H NMR, FI-IR, UV-vis, fluorescence spectra and zeta potential. Using ovalbumin (OVA) as a model antigen and FIP as an adjuvant for immunization, the formulations of FIP + OVA in different dosages could significantly promote the production of OVA-specific IgG in mice and prolong immune responses with acceptable safety.

引用

页码：2505 / 2514

页数：10