Injectable dual-scale mesoporous silica cancer vaccine enabling efficient delivery of antigen/adjuvant-loaded nanoparticles to dendritic cells recruited in local macroporous scaffold

Abstract

Despite the potential of nanoparticle-based vaccines, their therapeutic efficacy for cancer immunotherapy is limited. To elicit robust antigen-specific adaptive immune responses, antigen-loaded nanoparticles are employed for transport into host dendritic cells (DCs); however, only a minority of the nanoparticles can be engulfed by host DCs. Herein, an injectable dual-scale mesoporous silica vaccine consisting of mesoporous silica microrods (MSRs) coupled with mesoporous silica nanoparticles (MSNs) is introduced. The MSRs form a three-dimensional macroporous scaffold after injection, and the subsequent release of DC-recruiting chemokine loaded in the mesopores of MSRs leads to the recruitment of numerous DCs into the scaffold. Subsequently, MSNs co-loaded with an antigen and Toll-like receptor 9 agonist, which exist in interparticle space of the MSR scaffold, are internalized by the recruited DCs, leading to the generation of antigen-presenting activated DCs. Strikingly, the MSR-MSN dual-scale vaccine generates a significantly larger number of antigen-specific T cells and inhibits melanoma growth to a greater extent compared with a single MSR or MSN vaccine. Moreover, the dual-scale vaccine is synergized with an immune checkpoint inhibitor to inhibit tumor growth in tumor-bearing mice. The findings suggest that the MSR is a novel platform for delivering nanoparticle vaccines for the enhancement of cancer immunotherapy.