An enzyme-responsive and transformable PD-L1 blocking peptide-photosensitizer conjugate enables efficient photothermal immunotherapy for breast cancer
Mild photothermal therapy combined with immune checkpoint blockade has received increasing attention for the treatment of advanced or metastatic cancers due to its good therapeutic efficacy. However, it remains a challenge to facilely integrate the two therapies and make it potential for clinical tr...
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| Format: | Article |
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KeAi Communications Co., Ltd.
2023-04-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X22003620 |
| _version_ | 1827280295613693952 |
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| author | Yanan Sun Bochen Lyu Chang Yang Bing He Hua Zhang Xueqing Wang Qiang Zhang Wenbing Dai |
| author_facet | Yanan Sun Bochen Lyu Chang Yang Bing He Hua Zhang Xueqing Wang Qiang Zhang Wenbing Dai |
| author_sort | Yanan Sun |
| collection | DOAJ |
| description | Mild photothermal therapy combined with immune checkpoint blockade has received increasing attention for the treatment of advanced or metastatic cancers due to its good therapeutic efficacy. However, it remains a challenge to facilely integrate the two therapies and make it potential for clinical translation. This work designed a peptide-photosensitizer conjugate (PPC), which consisted of a PD-L1 antagonist peptide (CVRARTR), an MMP-2 specific cleavable sequence, a self-assembling motif, and the photosensitizer Purpurin 18. The single-component PPC can self-assemble into nanospheres which is suitable for intravenous injection. The PPC nanosphere is cleaved by MMP-2 when it accumulates in tumor sites, thereby initiating the cancer-specific release of the antagonist peptide. Simultaneously, the nanospheres gradually transform into co-assembled nanofibers, which promotes the retention of the remaining parts within the tumor. In vivo studies demonstrated that PPC nanospheres under laser irradiation promote the infiltration of cytotoxic T lymphocytes and maturation of DCs, which sensitize 4T1 tumor cells to immune checkpoint blockade therapy. Therefore, PPC nanospheres inhibit tumor growth efficiently both in situ and distally and blocked the formation of lung metastases. The present study provides a simple and efficient integrated strategy for breast cancer photoimmunotherapy. |
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| format | Article |
| id | doaj.art-61d8bf7745c84a7585bad96053a1f035 |
| institution | Directory Open Access Journal |
| issn | 2452-199X |
| language | English |
| last_indexed | 2024-04-24T08:34:28Z |
| publishDate | 2023-04-01 |
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| series | Bioactive Materials |
| spelling | doaj.art-61d8bf7745c84a7585bad96053a1f0352024-04-16T17:41:31ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2023-04-01224759An enzyme-responsive and transformable PD-L1 blocking peptide-photosensitizer conjugate enables efficient photothermal immunotherapy for breast cancerYanan Sun0Bochen Lyu1Chang Yang2Bing He3Hua Zhang4Xueqing Wang5Qiang Zhang6Wenbing Dai7Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China; Department of Pharmaceutics, School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang, 050017, ChinaBeijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, ChinaBeijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, ChinaBeijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, ChinaBeijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, ChinaBeijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China; Corresponding author.Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China; Corresponding author.Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China; Corresponding author.Mild photothermal therapy combined with immune checkpoint blockade has received increasing attention for the treatment of advanced or metastatic cancers due to its good therapeutic efficacy. However, it remains a challenge to facilely integrate the two therapies and make it potential for clinical translation. This work designed a peptide-photosensitizer conjugate (PPC), which consisted of a PD-L1 antagonist peptide (CVRARTR), an MMP-2 specific cleavable sequence, a self-assembling motif, and the photosensitizer Purpurin 18. The single-component PPC can self-assemble into nanospheres which is suitable for intravenous injection. The PPC nanosphere is cleaved by MMP-2 when it accumulates in tumor sites, thereby initiating the cancer-specific release of the antagonist peptide. Simultaneously, the nanospheres gradually transform into co-assembled nanofibers, which promotes the retention of the remaining parts within the tumor. In vivo studies demonstrated that PPC nanospheres under laser irradiation promote the infiltration of cytotoxic T lymphocytes and maturation of DCs, which sensitize 4T1 tumor cells to immune checkpoint blockade therapy. Therefore, PPC nanospheres inhibit tumor growth efficiently both in situ and distally and blocked the formation of lung metastases. The present study provides a simple and efficient integrated strategy for breast cancer photoimmunotherapy.http://www.sciencedirect.com/science/article/pii/S2452199X22003620Transformable nanomedicineSelf-assembled peptideImmune checkpoint blockadePhotothermal therapyPhotoimmunotherapy |
| spellingShingle | Yanan Sun Bochen Lyu Chang Yang Bing He Hua Zhang Xueqing Wang Qiang Zhang Wenbing Dai An enzyme-responsive and transformable PD-L1 blocking peptide-photosensitizer conjugate enables efficient photothermal immunotherapy for breast cancer Bioactive Materials Transformable nanomedicine Self-assembled peptide Immune checkpoint blockade Photothermal therapy Photoimmunotherapy |
| title | An enzyme-responsive and transformable PD-L1 blocking peptide-photosensitizer conjugate enables efficient photothermal immunotherapy for breast cancer |
| title_full | An enzyme-responsive and transformable PD-L1 blocking peptide-photosensitizer conjugate enables efficient photothermal immunotherapy for breast cancer |
| title_fullStr | An enzyme-responsive and transformable PD-L1 blocking peptide-photosensitizer conjugate enables efficient photothermal immunotherapy for breast cancer |
| title_full_unstemmed | An enzyme-responsive and transformable PD-L1 blocking peptide-photosensitizer conjugate enables efficient photothermal immunotherapy for breast cancer |
| title_short | An enzyme-responsive and transformable PD-L1 blocking peptide-photosensitizer conjugate enables efficient photothermal immunotherapy for breast cancer |
| title_sort | enzyme responsive and transformable pd l1 blocking peptide photosensitizer conjugate enables efficient photothermal immunotherapy for breast cancer |
| topic | Transformable nanomedicine Self-assembled peptide Immune checkpoint blockade Photothermal therapy Photoimmunotherapy |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X22003620 |
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