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  3. Epigenetic reprogramming of carrier free photodynamic modulator to activate tumor immunotherapy by EZH2 inhibition

Epigenetic reprogramming of carrier free photodynamic modulator to activate tumor immunotherapy by EZH2 inhibition

  • Biomaterials. 2022 Dec 7;293:121952. doi: 10.1016/j.biomaterials.2022.121952.
Linping Zhao 1,  Xiaona Rao 1,  Chuyu Huang 1,  Rongrong Zheng 1,  Renjiang Kong 2,  Zuxiao Chen 1,  Xiyong Yu 3,  Hong Cheng 4,  Shiying Li 5
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, PR China.
  • 2 Biomaterials Research Center, School of Biomedical Engineering, Southern Medical University, Guangzhou, 510515, PR China.
  • 3 Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, PR China. Electronic address: yuxycn@aliyun.com.
  • 4 Biomaterials Research Center, School of Biomedical Engineering, Southern Medical University, Guangzhou, 510515, PR China. Electronic address: chengh@smu.edu.cn.
  • 5 Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, PR China. Electronic address: lisy-sci@gzhmu.edu.cn.
PMID: 36502580 DOI: 10.1016/j.biomaterials.2022.121952
Abstract

Tumor cells are characterized by unlimited proliferation and escape of immune clearance, which are closely associated with the down regulation of surface antigens. In this work, a carrier free photodynamic modulator (CeTaz) is developed to improve immunosuppressive tumor microenvironment and promote the recognition of tumors by T cells by epigenetic reprogramming. Specifically, CeTaz is assembled by chlorine e6 (Ce6) and tazemetostat (Taz) through intermolecular interactions. Upon LIGHT irradiation, CeTaz is able to promote the generation of Reactive Oxygen Species (ROS) for a robust photodynamic therapy (PDT) to inhibit localized tumor growth. Meanwhile, the PDT also induces immunogenic cell death (ICD) to initiate immune response, leading to the activation of effector T cells. More importantly, CeTaz could inhibit the epigenetic regulator of EZH2 to suppress the methylation of H3K27, which would promote tumor cells to express MHC-I and release CXCL10. Consequently, the epigenetically reprogrammed tumor cells are readily recognized by effector T cells to enhance the antitumor immunity. Results indicate that the PDT activated immunotherapy of CeTaz could simultaneously inhibit the growth of primary and distant tumors with a low system toxicity. This study would advance the development of carrier free nanomedicine for precise treatment of metastatic tumor.

Keywords

Carrier free; EZH2 inhibition; Immunogenic cell death; Immunotherapy; Photodynamic therapy.

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