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Journal Article Review Epublish 1 citation

PubMed: 39635320 DOI: 10.1016/j.mtbio.2024.101346

A novel nanomedicine integrating ferroptosis and photothermal therapy, well-suitable for PD-L1-mediated immune checkpoint blockade.

Mater Today Bio 29:101346

Authors: Yujun Bao, Guanghao Li, Siqi Li, Haishui Zhou, Ziqing Yang, Zhiqiang Wang, Rui Yan, Changhong Guo, Yingxue Jin

Affiliations

  • Key Laboratory of Molecular Cytogenetics and Genetic Breeding of Heilongjiang Province, College of Life Science and Technology, Harbin Normal University, Harbin, 150025, China. Key Laboratory for Photonic and Electronic Bandgap Materials, Ministry of Education, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin, 150025, China.
  • Key Laboratory for Photonic and Electronic Bandgap Materials, Ministry of Education, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin, 150025, China.
  • Key Laboratory of Molecular Cytogenetics and Genetic Breeding of Heilongjiang Province, College of Life Science and Technology, Harbin Normal University, Harbin, 150025, China.
  • School of Basic Medical Sciences, Shandong University, Jinan, 250012, China.

Abstract

Immunotherapy based on immune checkpoint blockade has emerged as a promising treatment strategy; however, the therapeutic efficacy is limited by the immunosuppressive microenvironment. Here, we developed a novel immune-activated nanoparticle (Fc-SS-Fe/Cu) to address the issue of insufficient immune infiltration. Specifically, the structure of Fc-SS-Fe/Cu collapsed in response to the tumor microenvironment, the ferrocene and disulfide bonds and the released Fe/Cu ions can effectively generate ·OH and deplete GSH to increase oxidative stress, thereby inducing ferroptosis. Withal, the positive feedback mechanisms of "laser-triggered mild-temperature photothermal therapy (PTT), PTT accelerated ferroptosis and LPO accumulation, LPO mediated HSPs down-regulated to promote PTT," effectively triggers immunogenic cell death (ICD) in tumor cells, significantly enhancing their immunogenicity. Moreover, the O-generating ability induced by Fc-SS-Fe/Cu could reverse the hypoxic tumor microenvironment, and importantly, the expression of PD-L1 on tumor cell surfaces could be effectively downregulated by inhibiting the HIF-1 pathways, thereby augmenting the effect of anti-PD-L1 (PD-L1) therapy. Therefore, this study provides valuable strategies into enhancing PD-L1-mediated ICB therapy.

MeSH

Cells, Nanomedicine, Neoplasms, Ferroptosis, Photothermal Therapy, Therapeutics, Tumor Microenvironment

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