期刊
ACS NANO
卷 13, 期 7, 页码 7705-7715出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.9b01271
关键词
scale design; immune-targeted delivery; cancer immunotherapy; hydroxyapatite; rods
类别
资金
- JSPS KAKENHI [17K01399, 26750162]
- AIST project
- Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan
- Japan Society for the Promotion Science [15H04504]
- Strategic International Collaborative Research Program (SICORP)
- Cross-ministerial Strategic Innovation Promotion Program (SIP)
- Japan Agency for Medical Research and Development [17fk0210305h0003]
- Canon Foundation
- Nippon Sheet Glass Foundation for Materials Science and Engineering
- Grants-in-Aid for Scientific Research [15H04504, 17K01399, 26750162] Funding Source: KAKEN
Strengthening the antitumor immune response to surpass the activation energy barrier associated with the immunosuppressive tumor microenvironment is an active area of cancer immunotherapy. Emerging evidence suggests that delivery of immunostimulatory molecules with the aid of a carrier system is essential for cancer immunotherapy. However, the size-dependent effect of the delivery system on immune-targeted sites and anticancer immune responses is yet to be comprehensively understood. Herein, to clarify the size-dependent effect of the delivery system on the underlying anticancer immune mechanism, rod-shaped hydroxyapatite (HA) particles with lengths from 100 nm to 10 mu m are designed. HA rods stimulate anticancer immunity in a size-dependent manner. Shorter HA rods with lengths ranging from 100 to 500 nm promote antigen cellular uptake, dendritic cell (DC) maturation, and lymph node targeting antigen. In contrast, longer HA rods with lengths ranging from 500 nm to 10 mu m prolong antigen retention and increase DC accumulation. Medium-sized HA rods with a length of 500 nm, taking advantage of both short and long rods, show optimized antigen release and uptake, increased DCs accumulation and maturation, highest CD4(+) and CD8(+) T cell population, and the best anticancer immunity in vivo. The present study provides a rod-scale design strategy for an immune-targeted delivery system toward cancer immunotherapy in the future.
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