한빛사 논문
Thanh Loc Nguyen†,∇, Yue Yin¶,#,∇, Youngjin Choi†, Ji Hoon Jeong*,¶, and Jaeyun Kim*,†,‡,§,∥
†School of Chemical Engineering, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea
¶School of Pharmacy, Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea
‡Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea
§Biomedical Institute for Convergence at SKKU (BICS),Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea
∥Institute of Quantum Biophysics (IQB), Sungkyunkwan University (SKKU), Suwon 16419, Republic of Korea
#CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China
∇These authors contributed equally to this work.
*Correspondence should be addressed to J. H. J. and J. K.
Abstract
Deoxyribonucleic acid (DNA) vaccines are a promising cancer immunotherapy approach. However, effective delivery of DNA to antigen-presenting cells (e.g., dendritic cells (DCs)) for the induction of an adaptive immune response is limited. Conventional DNA delivery via intramuscular, intradermal, and subcutaneous injection by hypodermal needles shows a low potency and immunogenicity. Here, we propose the enhanced cancer DNA vaccine by direct transfection to the high number of DCs recruited into the chemoattractant-loaded injectable mesoporous silica microrods (MSRs). Subcutaneous administration of the MSRs mixed with tumor-antigen coding DNA polyplexes resulted in DC recruitment in the macroporous space of the scaffold formed by the spontaneous assembly of high-aspect-ratio MSRs, thereby allowing for enhanced cellular uptake of antigen-coded DNA by host DCs. The MSR scaffolds delivering the DNA vaccine trigger a more robust DC activation, antigen-specific CD8+ T cell response, and Th1 immune response compared to the bolus DNA vaccine. Additionally, the immunological memory can be induced with a single administration of the vaccine. The combination of the vaccination and antiprogrammed cell death-1 antibody significantly eliminates established lung metastasis. These results indicate that MSRs serve as a powerful platform for DNA vaccine delivery to DCs for effective cancer immunotherapy.
KEYWORDS:DNA vaccine, mesoporous silica, dendritic cells, cancer immunotherapy, three-dimensional scaffolds
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