Issue 10, 2024

Light-inducible nanodrug-mediated photodynamic and anti-apoptotic synergy for enhanced immunotherapy in triple-negative breast cancer

Abstract

Triple negative breast cancer (TNBC) exhibits limited responsiveness to immunotherapy owing to its immunosuppressive tumor microenvironment (TME). Here, a reactive oxygen species (ROS)-labile nanodrug encapsulating the photosensitizer Ce6 and Bcl-2 inhibitor ABT-737 was developed to provoke a robust immune response via the synergistic effect of photodynamic therapy (PDT) and the reversal of apoptosis resistance. Upon exposure to first-wave near-infrared laser irradiation, the generated ROS triggers PEG cleavage, facilitating the accumulation of the nanodrug at tumor region and endocytosis by tumor cells. Further irradiation leads to the substantial generation of cytotoxic ROS, initiating an immunogenic cell death (ICD) cascade, which prompts the maturation of dendritic cells (DCs) as well as the infiltration of T cells into the tumor site. Meanwhile, Bcl-2 inhibition counteracts apoptosis resistance, thereby amplifying PDT-induced ICD and bolstering antitumor immunity. As a result, the ROS-sensitive nanodrug demonstrates a potent inhibitory effect on tumor growth.

Graphical abstract: Light-inducible nanodrug-mediated photodynamic and anti-apoptotic synergy for enhanced immunotherapy in triple-negative breast cancer

Supplementary files

Article information

Article type
Paper
Submitted
17 Jan 2024
Accepted
16 Mar 2024
First published
02 Apr 2024

Biomater. Sci., 2024,12, 2639-2647

Light-inducible nanodrug-mediated photodynamic and anti-apoptotic synergy for enhanced immunotherapy in triple-negative breast cancer

J. Huang, X. Liu, M. Lin, Z. Xiao and X. Shuai, Biomater. Sci., 2024, 12, 2639 DOI: 10.1039/D4BM00083H

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