Citation: Rongrong Zheng, Zuxiao Chen, Qiuyuan Li, Ni Yang, Wenjun Zhang, Chuyu Huang, Linping Zhao, Xin Chen, Hong Cheng, Shiying Li. Endoplasmic reticulum targeting photodynamic oxidizer to boost anti-tumor immunity by intensifying immunogenic cell death in conjunction with IDO1 inhibition[J]. Chinese Chemical Letters, ;2025, 36(12): 110865. doi: 10.1016/j.cclet.2025.110865 shu

Endoplasmic reticulum targeting photodynamic oxidizer to boost anti-tumor immunity by intensifying immunogenic cell death in conjunction with IDO1 inhibition

Rongrong Zheng ^{a, b, 1} ,
Zuxiao Chen ^{d, 1} ,
Qiuyuan Li ^b ,
Ni Yang ^b ,
Wenjun Zhang ^a ,
Chuyu Huang ^b ,
Linping Zhao ^b ,
Xin Chen ^{a, *,} ,
Hong Cheng ^{c, *,} ,
Shiying Li ^{a, b, *,}

a.
Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China
b.
Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China
c.
Biomaterials Research Center, School of Biomedical Engineering, Southern Medical University, Guangzhou 510515, China
d.
Department of Breast Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510510, China

chen_xin1020@163.com

chengh@smu.edu.cn

lisy-sci@gzhmu.edu.cn

Received Date: 22 October 2024
Revised Date: 14 January 2025
Accepted Date: 15 January 2025
Available Online: 16 January 2025

Figures(7)

The inherent low immunogenicity and immunosuppressive metabolism of solid tumors significantly attenuate the immunotherapeutic effect and restrict the immune response. In this work, an endoplasmic reticulum (ER) targeting photodynamic oxidizer (designated as PhotoOx) is fabricated to boost the anti-tumor immunity by integrating photodynamic therapy (PDT) induced immunogenic cell death (ICD) with indoleamine 2,3-dioxygenase 1 (IDO1) inhibition. Among which, an ER targeting photosensitizer-peptide conjugate called PhotoPe is rationally designed for optimal functionality and amphiphilicity, which could self-assemble into nano-micelles co-delivering chlorin e6 and NLG919. PhotoOx exhibits a good stability to enable ER targeting drug delivery, which could induce ER rupture to intensify PDT induced ICD and release damage associated molecular patterns (DAMPs). Furthermore, PhotoOx could effectively initiate immunological cascades, leading to the suppression of regulatory T cells (Tregs) and activation of CD8⁺ T cells when combines with IDO inhibition. Furthermore, the multi-synergistic effects of PhotoOx activate a robust systemic anti-tumor immune response, resulting in the eradication of lung and liver metastases. Such a medication strategy might inspire the rational design of biomedicine for precise drug delivery, which also provides a sophisticated mechanism for addressing the challenges of solid tumor treatment.
- Chimeric peptide,
- Endoplasmic reticulum targeting,
- Photodynamic therapy,
- Indoleamine 2,3-dioxygenase,
- Immunotherapy
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