2. Academic Validation
  3. A theranostic photosensitizer-conjugated albumin co-loading with resiquimod for cancer-targeted imaging and robust photo-immunotherapy

A theranostic photosensitizer-conjugated albumin co-loading with resiquimod for cancer-targeted imaging and robust photo-immunotherapy

  • Pharmacol Res. 2024 Dec:210:107489. doi: 10.1016/j.phrs.2024.107489.
Xu Tan 1,  Yu Wang 1,  Lei Long 1,  Hongdan Chen 2,  Langfan Qu 1,  Xiaohui Cao 1,  Huijuan Li 1,  Zelin Chen 3,  Shenglin Luo 4,  Chunmeng Shi 5
Affiliations

Affiliations

  • 1 Institute of Rocket Force Medicine, State Key Laboratory of Trauma and Chemical Poisoning, College of Preventive Medicine, Army Medical University, Gaotanyan Street 30, Chongqing 400038, China.
  • 2 Department of Breast and Thyroid Surgery, Chongqing General Hospital, Xingguang Road 118, Chongqing 401121, China.
  • 3 Institute of Rocket Force Medicine, State Key Laboratory of Trauma and Chemical Poisoning, College of Preventive Medicine, Army Medical University, Gaotanyan Street 30, Chongqing 400038, China. Electronic address: czlwx1811@163.com.
  • 4 Institute of Combined Injury, State Key Laboratory of Trauma and Chemical Poisoning, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Army Medical University, Gaotanyan Street 30, Chongqing 400038, China. Electronic address: luosl@tmmu.edu.cn.
  • 5 Institute of Rocket Force Medicine, State Key Laboratory of Trauma and Chemical Poisoning, College of Preventive Medicine, Army Medical University, Gaotanyan Street 30, Chongqing 400038, China. Electronic address: shicm@tmmu.edu.cn.
PMID: 39510147 DOI: 10.1016/j.phrs.2024.107489
Abstract

Cancer Immunotherapy remains a low immune response rate in clinic because of dominant immunosuppressive tumor microenvironment (TME) and lack of effective drug to specifically remodel the TME. In this work, we introduced a tumor-seeking human serum albumin (HSA) based delivery platform by covalently conjugating with a tumor-targeting near-infrared (NIR) photosensitizer (IR-DBI) and non-covalently loading of immune modulator Resiquimod (R848). HSA exhibited tumor-preferential accumulation after covalent conjugation with IR-DBI. Meanwhile, HSA restricted the rotation of IR-DBI, narrowed the HOMO-LUMO energy gap, significantly enhanced fluorescent intensity and dual-modal phototherapy (PTT/PDT). The enhanced phototherapeutic effect further induced robust ICD effect. More importantly, non-covalent loading of R848 could be released from HSA at tumor sites by laser irradiation-induced heat. The in-situ release of R848 in TME efficiently promoted the maturation of DC cells and repolarized M2 macrophages to M1 macrophages. Consequently, robust photo-induced antitumor immunity was triggered in the different mice models bearing primary and distant tumors or lung metastasis, which was further enhanced by combining with CTLA-4 blockade therapy. Taken together, this work may present a versatile albumin composite which exhibits tumor-preferential accumulation and imaging-guided PDT/PTT/immunotherapy.

Keywords

CTLA-4 blockade therapy; Cancer immunotherapy; Dual-modal phototherapy; Human serum albumin; Tumor microenvironment.

Figures
Products