한빛사 논문
Thanh Loc Nguyena, Bong Geun Chaa, Youngjin Choia, Jihye Ima, Jaeyun Kima,b,c,d,*
aSchool of Chemical Engineering, Sungkyunkwan University (SKKU), Suwon, 16419, Republic of Korea
bDepartment of Health Sciences and Technology, Samsung Advanced Institute for Health Science & Technology (SAIHST), Sungkyunkwan University (SKKU), Suwon, 16419, Republic of Korea
cBiomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University (SKKU), Suwon, 16419, Republic of Korea
dInstitute of Quantum Biophysics (IQB), Sungkyunkwan University (SKKU), Suwon, 16419, Republic of Korea
*Corresponding author.
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.
Keywords : Cancer vaccine; Cancer immunotherapy; Mesoporous silica; 3D scaffold; Dendritic cells
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