A theranostic photosensitizer-conjugated albumin co-loading with resiquimod for cancer-targeted imaging and robust photo-immunotherapy
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...
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Elsevier
2024-12-01
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| Series: | Pharmacological Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661824004341 |
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| author | Xu Tan Yu Wang Lei Long Hongdan Chen Langfan Qu Xiaohui Cao Huijuan Li Zelin Chen Shenglin Luo Chunmeng Shi |
| author_facet | Xu Tan Yu Wang Lei Long Hongdan Chen Langfan Qu Xiaohui Cao Huijuan Li Zelin Chen Shenglin Luo Chunmeng Shi |
| author_sort | Xu Tan |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-6bb1c96b5a784a79828a5d69900fbed4 |
| institution | OA Journals |
| issn | 1096-1186 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj-art-6bb1c96b5a784a79828a5d69900fbed42025-08-20T01:57:51ZengElsevierPharmacological Research1096-11862024-12-0121010748910.1016/j.phrs.2024.107489A theranostic photosensitizer-conjugated albumin co-loading with resiquimod for cancer-targeted imaging and robust photo-immunotherapyXu Tan0Yu Wang1Lei Long2Hongdan Chen3Langfan Qu4Xiaohui Cao5Huijuan Li6Zelin Chen7Shenglin Luo8Chunmeng Shi9Institute of Rocket Force Medicine, State Key Laboratory of Trauma and Chemical Poisoning, College of Preventive Medicine, Army Medical University, Gaotanyan Street 30, Chongqing 400038, ChinaInstitute of Rocket Force Medicine, State Key Laboratory of Trauma and Chemical Poisoning, College of Preventive Medicine, Army Medical University, Gaotanyan Street 30, Chongqing 400038, ChinaInstitute of Rocket Force Medicine, State Key Laboratory of Trauma and Chemical Poisoning, College of Preventive Medicine, Army Medical University, Gaotanyan Street 30, Chongqing 400038, ChinaDepartment of Breast and Thyroid Surgery, Chongqing General Hospital, Xingguang Road 118, Chongqing 401121, ChinaInstitute of Rocket Force Medicine, State Key Laboratory of Trauma and Chemical Poisoning, College of Preventive Medicine, Army Medical University, Gaotanyan Street 30, Chongqing 400038, ChinaInstitute of Rocket Force Medicine, State Key Laboratory of Trauma and Chemical Poisoning, College of Preventive Medicine, Army Medical University, Gaotanyan Street 30, Chongqing 400038, ChinaInstitute of Rocket Force Medicine, State Key Laboratory of Trauma and Chemical Poisoning, College of Preventive Medicine, Army Medical University, Gaotanyan Street 30, Chongqing 400038, ChinaInstitute 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; Corresponding authors.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; Corresponding authors.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; Corresponding authors.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.http://www.sciencedirect.com/science/article/pii/S1043661824004341Human serum albuminDual-modal phototherapyCancer immunotherapyTumor microenvironmentCTLA-4 blockade therapy |
| spellingShingle | Xu Tan Yu Wang Lei Long Hongdan Chen Langfan Qu Xiaohui Cao Huijuan Li Zelin Chen Shenglin Luo Chunmeng Shi A theranostic photosensitizer-conjugated albumin co-loading with resiquimod for cancer-targeted imaging and robust photo-immunotherapy Pharmacological Research Human serum albumin Dual-modal phototherapy Cancer immunotherapy Tumor microenvironment CTLA-4 blockade therapy |
| title | A theranostic photosensitizer-conjugated albumin co-loading with resiquimod for cancer-targeted imaging and robust photo-immunotherapy |
| title_full | A theranostic photosensitizer-conjugated albumin co-loading with resiquimod for cancer-targeted imaging and robust photo-immunotherapy |
| title_fullStr | A theranostic photosensitizer-conjugated albumin co-loading with resiquimod for cancer-targeted imaging and robust photo-immunotherapy |
| title_full_unstemmed | A theranostic photosensitizer-conjugated albumin co-loading with resiquimod for cancer-targeted imaging and robust photo-immunotherapy |
| title_short | A theranostic photosensitizer-conjugated albumin co-loading with resiquimod for cancer-targeted imaging and robust photo-immunotherapy |
| title_sort | theranostic photosensitizer conjugated albumin co loading with resiquimod for cancer targeted imaging and robust photo immunotherapy |
| topic | Human serum albumin Dual-modal phototherapy Cancer immunotherapy Tumor microenvironment CTLA-4 blockade therapy |
| url | http://www.sciencedirect.com/science/article/pii/S1043661824004341 |
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