A Shear-Thinning Biomaterial-Mediated Immune Checkpoint Blockade

Qingzhi Wu, Moyuan Qu, Han Jun Kim, Xingwu Zhou, Xing Jiang, Yi Chen, Jixiang Zhu, Li Ren, Tyler Wolter, Heemin Kang, Chun Xu, Zhen Gu, Wujin Sun, Ali Khademhosseini

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Systemic administration of immune checkpoint blockade agents can activate the anticancer activity of immune cells; however, the response varies from patient to patient and presents potential off-target toxicities. Local administration of immune checkpoint inhibitors (ICIs) can maximize therapeutic efficacies while reducing side effects. This study demonstrates a minimally invasive strategy to locally deliver anti-programmed cell death protein 1 (anti-PD-1) with shear-thinning biomaterials (STBs). ICI can be injected into tumors when loaded in STBs (STB-ICI) composed of gelatin and silicate nanoplatelets (Laponite). The release of ICI from STB was mainly affected by the Laponite percentage in STBs and pH of the local microenvironment. Low Laponite content and acidic pH can induce ICI release. In a murine melanoma model, the injection of STB-ICI significantly reduced tumor growth and increased CD8+ T cell level in peripheral blood. STB-ICI also induced increased levels of tumor-infiltrating CD4+ helper T cells, CD8+ cytotoxic T cells, and tumor death. The STB-based minimally invasive strategy provides a simple and efficient approach to deliver ICIs locally.

Original languageEnglish
Pages (from-to)35309-35318
Number of pages10
JournalACS Applied Materials and Interfaces
Volume14
Issue number31
DOIs
Publication statusPublished - 2022 Aug 10

Keywords

  • cancer immunotherapy
  • drug delivery
  • immune checkpoint blockade
  • shear-thinning biomaterials
  • sustained release

ASJC Scopus subject areas

  • Materials Science(all)

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