Extra-Large Pore Mesoporous Silica Nanoparticles Enabling Co-Delivery of High Amounts of Protein Antigen and Toll-like Receptor 9 Agonist for Enhanced Cancer Vaccine Efficacy

被引:190
作者
Cha, Bong Geun [1 ]
Jeong, Ji Hoon [2 ]
Kim, Jaeyun [1 ,3 ,4 ]
机构
[1] Sungkyunkwan Univ SKKU, Sch Chem Engn, Suwon 16419, South Korea
[2] Sungkyunkwan Univ SKKU, Sch Pharm, Suwon 16419, South Korea
[3] Sungkyunkwan Univ SKKU, Dept Hlth Sci & Technol, SAIHST, Suwon 16419, South Korea
[4] Sungkyunkwan Univ SKKU, Biomed Inst Convergence SKKU BICS, Suwon 16419, South Korea
基金
新加坡国家研究基金会;
关键词
DENDRITIC-CELL IMMUNOTHERAPY; MESENCHYMAL STEM-CELLS; IN-VIVO; CROSS-PRESENTATION; DRUG-DELIVERY; GENE DELIVERY; NANOSPHERES; IMMUNITY; NANOCRYSTALS; STIMULATION;
D O I
10.1021/acscentsci.8b00035
中图分类号
O6 [化学];
学科分类号
070301 [无机化学];
摘要
Cancer vaccine aims to invoke antitumor adaptive immune responses to detect and eliminate tumors. However, the current dendritic cells (DCs)-based cancer vaccines have several limitations that are mostly derived from the ex vivo culture of patient DCs. To circumvent the limitations, direct activation and maturation of host DCs using antigen-carrying materials, without the need for isolation of DCs from patients, are required. In this study, we demonstrate the synthesis of extra-large pore mesoporous silica nanoparticles (XL-MSNs) and their use as a prophylactic cancer vaccine through the delivery of cancer antigen and danger signal to host DCs in the draining lymph nodes. Extralarge pores of approximately 25 nm and additional surface modification of XLMSNs resulted in significantly higher loading of antigen protein and toll-like receptor 9 (TLR9) agonist compared with conventional small-pore MSNs. In vitro study showed the enhanced activation and antigen presentation of DCs and increased secretion of proinflammatory cytokines. In vivo study demonstrated efficient targeting of XL-MSNs co-delivering antigen and TLR9 agonist to draining lymph nodes, induction of antigen-specific cytotoxic T lymphocytes (CTLs), and suppression of tumor growth after vaccination. Furthermore, significant prevention of tumor growth after tumor rechallenge of the vaccinated tumor-free mice resulted, which was supported by a high level of memory T cells. These findings suggest that mesoporous silica nanoparticles with extra-large pores can be used as an attractive platform for cancer vaccines.
引用
收藏
页码:484 / 492
页数:9
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