Visible-Light-Triggered Prodrug Nanoparticles Combine Chemotherapy and Photodynamic Therapy to Potentiate Checkpoint Blockade Cancer Immunotherapy

Jiwoong Choi, Man Kyu Shim, Suah Yang, Hee Sook Hwang, Hanhee Cho, Jeongrae Kim, Wan Su Yun, Yujeong Moon, Jinseong Kim, Hong Yeol Yoon, Kwangmeyung Kim

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

Immune checkpoint blockade is a promising approach for cancer immunotherapy, but many patients do not respond due to the immunosuppressive tumor microenvironment (ITM). Herein, we propose visible-light-triggered prodrug nanoparticles (LT-NPs) for reversing ITM into high immunogenic tumors to potentiate checkpoint blockade immunotherapy. The photosensitizer (verteporfin; VPF), cathepin B-specific cleavable peptide (FRRG), and doxorubicin (DOX) conjugates are self-assembled into LT-NPs without any additional carrier material. The LT-NPs are specifically cleaved to VPF and DOX in cathepsin B-overexpressing cancer cells, thereby inducing cancer-specific cytotoxicity and immunogenic cell death (ICD) upon visible light irradiation. In tumor models, LT-NPs highly accumulate within tumors via the enhanced permeability and retention effect, and photochemotherapy of VPF and DOX induces effective ICD and maturation of dendritic cells to stimulate cross-presentation of cancer-antigens to T cells. Furthermore, LT-NPs with PD-L1 blockade greatly inhibit tumor growth, tumor recurrence, and lung metastasis by initiating a strong antitumor immune response. The photochemotherapy by LT-NPs provides a promising strategy for effective checkpoint blockade immunotherapy.

Original languageEnglish
Pages (from-to)12086-12098
Number of pages13
JournalACS nano
Volume15
Issue number7
DOIs
Publication statusPublished - 2021 Jul 27

Keywords

  • antitumor immune response
  • cancer immunotherapy
  • immune checkpoint blockade
  • light-triggered prodrug
  • photochemotherapy

ASJC Scopus subject areas

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

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