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  3. A Type I/II Photosensitizer with Lysosome-Targeting Capabilities Induces Immunogenic Cell Death in Cancer Cells to Enhance Tumor Immunotherapy

A Type I/II Photosensitizer with Lysosome-Targeting Capabilities Induces Immunogenic Cell Death in Cancer Cells to Enhance Tumor Immunotherapy

  • ACS Nano. 2026 Mar 10;20(9):7438-7453. doi: 10.1021/acsnano.5c14676.
Ping Jiang 1,  Le Wang 1,  Ruming Jiang 2,  Rui Zeng 3,  Weiye Huang 3,  Guanquan Mao 3,  Tao Liu 4,  Ben Zhong Tang 5,  Haiping Cai 6,  Zujin Zhao 7,  Yan Mei 3
Affiliations

Affiliations

  • 1 Department of Laboratory Medicine, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, South China University of Technology, Guangzhou 510180, China.
  • 2 School of Materials and Energy, Foshan University, Foshan 528000, China.
  • 3 Department of Pathology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China.
  • 4 Department of Otolaryngology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China.
  • 5 Guangdong Basic Research Center of Excellence for Aggregate Science, School of Science and Engineering, Shenzhen Institute of Aggregate Science and Technology, The Chinese University of Hong Kong (CUHK-Shenzhen), Shenzhen 518172, China.
  • 6 Department of Neurosurgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China.
  • 7 State Key Laboratory of Luminescent Materials and Devices, Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, South China University of Technology, Guangzhou 510640, China.
PMID: 41721786 DOI: 10.1021/acsnano.5c14676
Abstract

The immunosuppressive microenvironment initially hinders tumors' response to immunotherapy. Enhancing immunotherapy outcomes can be achieved through a strategy that efficiently activates dendritic cells (DCs), T cells, and macrophages within the tumor microenvironment (TME). This study develops a Photosensitizer named CPBPDPN-TPA, which is based on dibenzo[a,c]phenazine (DP) and shows an aggregation-induced emission (AIE) and delayed fluorescence. It effectively produces both type I and type II Reactive Oxygen Species (ROS), making it a promising option for photodynamic therapy (PDT). CPBPDPN-TPA selectively accumulates in lysosomes and induces significant lysosomal damage in tumor cells when exposed to white light irradiation. This damage leads to both Apoptosis and immunogenic cell death (ICD) via ROS, ultimately preventing tumor progression. Importantly, CPBPDPN-TPA also allows the reprogramming of the TME, inducing CD8+ T-cell infiltration, macrophage M1 polarization, and dendritic cell maturation via activating the STING signaling pathway. The combination of PDT and anti-PD-1 treatment creates a synergistic effect that significantly inhibits tumor growth in vivo. In conclusion, this study proposes a model that improves immunotherapy by combining PDT and PD-1 blockade, greatly enhancing antitumor immunity and inhibiting tumor growth effectively.

Keywords

PD-1 blockade; aggregation-induced emission; immunogenic cell death; lysosome-targeting; photodynamic therapy; reactive oxygen species.

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