Anti-PD-L1 peptide-conjugated prodrug nanoparticles for targeted cancer immunotherapy combining PD-L1 blockade with immunogenic cell death

Yujeong Moon, Man Kyu Shim, Jiwoong Choi, Suah Yang, Jinseong Kim, Wan Su Yun, Hanhee Cho, Jung Yeon Park, Yongju Kim, Joon Kyung Seong, Kwangmeyung Kim

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Rationale: Cancer immunotherapy combining immune checkpoint blockade (ICB) with chemotherapeutic drugs has provided significant clinical advances. However, such combination therapeutic regimen has suffered from severe toxicity of both drugs and low response rate of patients. In this study, we propose anti-PD-L1 peptide-conjugated prodrug nanoparticles (PD-NPs) to overcome these obstacles of current cancer immunotherapy. Methods: The functional peptide, consisted of anti-PD-L1 peptide and cathepsin B-specific cleavable peptide, is conjugated to a doxorubicin (DOX), resulting in prodrug nanoparticles of PD-NPs via intermolecular interactions. The antitumor efficacy and immune responses with minimal side effects by PD-NPs combining PD-L1 blockade and ICD are evaluated in breast tumor models. Results: The PD-NPs are taken up by PD-L1 receptor-mediated endocytosis and then induce ICD in cancer cells by DOX release. Concurrently, PD-L1 blockade by PD-NPs disrupt the immune-suppressing pathway of cancer cells, resulting in proliferation and reinvigoration of T lymphocytes. In tumor models, PD-NPs accumulate within tumor tissues via enhanced permeability and retention (EPR) effect and induce immune-responsive tumors by recruiting a large amount of immune cells. Conclusions: Collectively, targeted tumor delivery of anti-PD-L1 peptide and DOX via PD-NPs efficiently inhibit tumor progression with minimal side effects.

Original languageEnglish
Pages (from-to)1919-2014
Number of pages96
JournalTheranostics
Volume12
Issue number5
DOIs
Publication statusPublished - 2022

Keywords

  • Antitumor immune response
  • Cancer immunotherapy
  • Drug delivery
  • Immune checkpoint blockade
  • Prodrug nanoparticle

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

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