Sting Agonist-Loaded Mesoporous Manganese-Silica Nanoparticles for Vaccine Applications

Authors

Cheng Xu
Hannah E Dobson
Mengjie Yu
Wang Gong
Xiaoqi Sun
Kyung Soo Park
Andrew Kennedy
Xingwu Zhou
Jin Xu
Yao Xu
Andrew W Tai
Yu Leo Lei
James J Moon

Publication Date

5-1-2023

Journal

Journal of Controlled Release

Abstract

Cyclic dinucleotides (CDNs), as one type of Stimulator of Interferon Genes (STING) pathway agonist, have shown promising results for eliciting immune responses against cancer and viral infection. However, the suboptimal drug-like properties of conventional CDNs, including their short in vivo half-life and poor cellular permeability, compromise their therapeutic efficacy. In this study, we have developed a manganese-silica nanoplatform (MnOx@HMSN) that enhances the adjuvant effects of CDN by achieving synergy with Mn2+ for vaccination against cancer and SARS-CoV-2. MnOx@HMSN with large mesopores were efficiently co-loaded with CDN and peptide/protein antigens. MnOx@HMSN(CDA) amplified the activation of the STING pathway and enhanced the production of type-I interferons and other proinflammatory cytokines from dendritic cells. MnOx@HMSN(CDA) carrying cancer neoantigens elicited robust antitumor T-cell immunity with therapeutic efficacy in two different murine tumor models. Furthermore, MnOx@HMSN(CDA) loaded with SARS-CoV-2 antigen achieved strong and durable (up to one year) humoral immune responses with neutralizing capability. These results demonstrate that MnOx@HMSN(CDA) is a versatile nanoplatform for vaccine applications.

Keywords

Humans, Animals, Mice, Manganese, Silicon Dioxide, COVID-19, SARS-CoV-2, Vaccines, Nanoparticles, Hereditary Sensory and Motor Neuropathy, Immunotherapy

Comments

Supplementary Materials

PMID: 36948420