Rod-Scale Design Strategies for Immune-Targeted Delivery System toward Cancer Immunotherapy

Xiupeng Wang, Shu Ihara, Xia Li, Atsuo Ito, Yu Sogo, Yohei Watanabe, Atsushi Yamazaki, Noriko M. Tsuji, Tadao Ohno

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)7705-7715
Number of pages11
JournalACS Nano
Volume13
Issue number7
DOIs
Publication statusPublished - 2019 Jul 23

Keywords

  • cancer immunotherapy
  • hydroxyapatite
  • immune-targeted delivery
  • rods
  • scale design

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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  • Cite this

    Wang, X., Ihara, S., Li, X., Ito, A., Sogo, Y., Watanabe, Y., Yamazaki, A., Tsuji, N. M., & Ohno, T. (2019). Rod-Scale Design Strategies for Immune-Targeted Delivery System toward Cancer Immunotherapy. ACS Nano, 13(7), 7705-7715. https://doi.org/10.1021/acsnano.9b01271