2. Academic Validation
  3. Chlorin e6 and Regorafenib Assemblies to Boost Photodynamic Immunotherapy through PD-L1 Downregulation and Tumor-Associated Macrophage Reprogramming

Chlorin e6 and Regorafenib Assemblies to Boost Photodynamic Immunotherapy through PD-L1 Downregulation and Tumor-Associated Macrophage Reprogramming

  • ACS Appl Mater Interfaces. 2026 Apr 1;18(12):17602-17615. doi: 10.1021/acsami.6c01869.
Chu-Yu Huang 1,  Yun Ye 1,  Shao-Yi Chen 2,  Zu-Xiao Chen 3,  Wen-Feng Zhu 4,  A-Li Chen 5,  Ying-Ling Miao 1,  Shi-Ying Li 1
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, the School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, P. R. China.
  • 2 Thoracic Oncology Institute, Department of Thoracic Surgery, Peking University People's Hospital, Beijing 100044, P. R. China.
  • 3 Sun Yat-Sen University Cancer Center, Sun Yat-sen University Cancer Institute, National Key Laboratory of Southern China for Cancer Prevention and Treatment, Guangzhou 510062, P. R. China.
  • 4 Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, P. R. China.
  • 5 Center for Drug Research and Development, Guangdong Provincial Key Laboratory of Advanced Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou 510006, P. R. China.
PMID: 41855525 DOI: 10.1021/acsami.6c01869
Abstract

The effectiveness of immunotherapy is significantly limited by the inherently low immunogenicity and immunosuppressive phenotypes of tumors. To address this challenge, we develop assemblies composed of chlorin e6 and regorafenib (designated as CeRe), which combine photodynamic therapy (PDT) with immune regulatiing functions. CeRe exhibits uniform nanoscale distribution and good stability without requiring additional carriers. Upon light activation, CeRe eradicate tumor cells via PDT-induced Reactive Oxygen Species (ROS) while simultaneously triggering immunogenic cell death (ICD). Furthermore, CeRe downregulates PD-L1 expression in tumor cells, promotes macrophage polarization, and relieves the immunosuppressive tumor microenvironment (TME). These synergistic immunomodulatory effects substantially improve tumor responsiveness to αPD-L1 treatment, leading to the effective inhibition of both primary and metastatic tumor growth. Collectively, this work presents a carrier-free nanodrug assembly strategy with multifaceted mechanisms, offering a promising approach for precise tumor therapy and metastasis suppression.

Keywords

PD-L1; drug assemblies; drug delivery; immunosuppressive microenvironment; photodynamic therapy.

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