期刊
BIOMATERIALS
卷 239, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2020.119859
关键词
Cancer vaccine; Cancer immunotherapy; Mesoporous silica; 3D scaffold; Dendritic cells
资金
- National Research Foundation (NRF) under the Ministry of Science and ICT, Republic of Korea [2015R1A2A2A01005548, 2010-0027955]
- National Research Foundation of Korea [2015R1A2A2A01005548] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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.
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