TY - JOUR
T1 - Rod-Scale Design Strategies for Immune-Targeted Delivery System toward Cancer Immunotherapy
AU - Wang, Xiupeng
AU - Ihara, Shu
AU - Li, Xia
AU - Ito, Atsuo
AU - Sogo, Yu
AU - Watanabe, Yohei
AU - Yamazaki, Atsushi
AU - Tsuji, Noriko M.
AU - Ohno, Tadao
N1 - Funding Information:
We thank Ms. H. Sugino, Ms. K. Yoshiyuki, Dr. X. Li, and Dr. J. Li for their technical assistance. We thank Prof. K. Tsuboi at the University of Tsukuba for fruitful discussions. This study was supported in part by Nippon Sheet Glass Foundation for Materials Science and Engineering, JSPS KAKENHI Grant Nos. 17K01399 and 26750162, AIST project, and the NIMS Molecule & Material Synthesis Platform in “Nanotechnology Platform Project” operated by the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan. N.M.T. thanks the Japan Society for the Promotion Science 15H04504 (JSPS), a Grant-in-Aid from Strategic International Collaborative Research Program (SICORP), a Grant-in-Aid from Cross-ministerial Strategic Innovation Promotion Program (SIP), the Research Program on Hepatitis from Japan Agency for Medical Research and Development 17fk0210305h0003 (AMED), and a Grant-in-Aid from the Canon Foundation.
Publisher Copyright:
© 2019 American Chemical Society.
PY - 2019/7/23
Y1 - 2019/7/23
N2 - 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 μm 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 μm 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.
AB - 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 μm 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 μm 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.
KW - cancer immunotherapy
KW - hydroxyapatite
KW - immune-targeted delivery
KW - rods
KW - scale design
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U2 - 10.1021/acsnano.9b01271
DO - 10.1021/acsnano.9b01271
M3 - Article
C2 - 31241885
AN - SCOPUS:85070486013
SN - 1936-0851
VL - 13
SP - 7705
EP - 7715
JO - ACS Nano
JF - ACS Nano
IS - 7
ER -
