Senescence-associated secretory phenotype regulation by dual drug delivery biomimetic nanoplatform for enhanced tumor chemotherapy
Many chemotherapies, which are still the main clinical treatment for primary tumors, will induce persistent DNA damage in non-tumor stromal cells, especially cancer-associated fibroblasts (CAFs), and activate them to secrete senescence-associated secretory phenotype (SASP). The transition could furt...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-09-01
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| Series: | Molecular Therapy: Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950329924000985 |
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| author | Anni Wang Shiyi Li Ru Zhang Xing Chen Ying Zhu Jiaxuan Xia Jianxin Wang |
| author_facet | Anni Wang Shiyi Li Ru Zhang Xing Chen Ying Zhu Jiaxuan Xia Jianxin Wang |
| author_sort | Anni Wang |
| collection | DOAJ |
| description | Many chemotherapies, which are still the main clinical treatment for primary tumors, will induce persistent DNA damage in non-tumor stromal cells, especially cancer-associated fibroblasts (CAFs), and activate them to secrete senescence-associated secretory phenotype (SASP). The transition could further result in the formation of tumor immunosuppressive microenvironment and cause drug resistance of neighboring tumor cells. To solve this dilemma, a multi-functional biomimetic drug delivery system (named mPtP@Lipo) was rationally developed by combining CAFs reshaper ginsenoside 20(S)-protopanaxadiol (PPD) and cisplatin prodrug (PtLA) to inhibit tumor progression and the formation of SASP. To achieve effective delivery of these molecules deep into the desmoplastic tumor, fibroblast membrane was fused with liposomes as a targeting carrier. In vitro and in vivo results showed that mPtP@Lipo could penetrate deep into the tumor, reverse CAFs phenotype and inhibit SASP formation, which then blocked the immunosuppressive progress and thus reinforced anti-tumor immune response. The combination of chemotherapeutics and CAFs regulator could achieve both tumor inhibition and tumor immune microenvironment remodeling. In conclusion, mPtP@Lipo provides a promising strategy for the comprehensive stromal-desmoplastic tumor treatment. |
| format | Article |
| id | doaj-art-946ceffd9932460d96d0a69e6824f967 |
| institution | Kabale University |
| issn | 2950-3299 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncology |
| spelling | doaj-art-946ceffd9932460d96d0a69e6824f9672024-11-24T04:15:46ZengElsevierMolecular Therapy: Oncology2950-32992024-09-01323200856Senescence-associated secretory phenotype regulation by dual drug delivery biomimetic nanoplatform for enhanced tumor chemotherapyAnni Wang0Shiyi Li1Ru Zhang2Xing Chen3Ying Zhu4Jiaxuan Xia5Jianxin Wang6Department of Pharmaceutics, School of Pharmacy, Fudan University and Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai 201203, ChinaDepartment of Pharmaceutics, School of Pharmacy, Fudan University and Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai 201203, ChinaDepartment of Pharmaceutics, School of Pharmacy, Fudan University and Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai 201203, ChinaDepartment of Pharmaceutics, School of Pharmacy, Fudan University and Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai 201203, ChinaDepartment of Pharmaceutics, School of Pharmacy, Fudan University and Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai 201203, China; Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, ChinaDepartment of Pharmaceutics, School of Pharmacy, Fudan University and Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai 201203, ChinaDepartment of Pharmaceutics, School of Pharmacy, Fudan University and Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai 201203, China; Corresponding author: Jianxin Wang, Department of Pharmaceutics, School of Pharmacy, Fudan University and Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai 201203, China.Many chemotherapies, which are still the main clinical treatment for primary tumors, will induce persistent DNA damage in non-tumor stromal cells, especially cancer-associated fibroblasts (CAFs), and activate them to secrete senescence-associated secretory phenotype (SASP). The transition could further result in the formation of tumor immunosuppressive microenvironment and cause drug resistance of neighboring tumor cells. To solve this dilemma, a multi-functional biomimetic drug delivery system (named mPtP@Lipo) was rationally developed by combining CAFs reshaper ginsenoside 20(S)-protopanaxadiol (PPD) and cisplatin prodrug (PtLA) to inhibit tumor progression and the formation of SASP. To achieve effective delivery of these molecules deep into the desmoplastic tumor, fibroblast membrane was fused with liposomes as a targeting carrier. In vitro and in vivo results showed that mPtP@Lipo could penetrate deep into the tumor, reverse CAFs phenotype and inhibit SASP formation, which then blocked the immunosuppressive progress and thus reinforced anti-tumor immune response. The combination of chemotherapeutics and CAFs regulator could achieve both tumor inhibition and tumor immune microenvironment remodeling. In conclusion, mPtP@Lipo provides a promising strategy for the comprehensive stromal-desmoplastic tumor treatment.http://www.sciencedirect.com/science/article/pii/S2950329924000985MT: Regular Issuecancer-associated fibroblastschemotherapyliposomessenescence-associated secretory phenotypetumor microenvironment |
| spellingShingle | Anni Wang Shiyi Li Ru Zhang Xing Chen Ying Zhu Jiaxuan Xia Jianxin Wang Senescence-associated secretory phenotype regulation by dual drug delivery biomimetic nanoplatform for enhanced tumor chemotherapy Molecular Therapy: Oncology MT: Regular Issue cancer-associated fibroblasts chemotherapy liposomes senescence-associated secretory phenotype tumor microenvironment |
| title | Senescence-associated secretory phenotype regulation by dual drug delivery biomimetic nanoplatform for enhanced tumor chemotherapy |
| title_full | Senescence-associated secretory phenotype regulation by dual drug delivery biomimetic nanoplatform for enhanced tumor chemotherapy |
| title_fullStr | Senescence-associated secretory phenotype regulation by dual drug delivery biomimetic nanoplatform for enhanced tumor chemotherapy |
| title_full_unstemmed | Senescence-associated secretory phenotype regulation by dual drug delivery biomimetic nanoplatform for enhanced tumor chemotherapy |
| title_short | Senescence-associated secretory phenotype regulation by dual drug delivery biomimetic nanoplatform for enhanced tumor chemotherapy |
| title_sort | senescence associated secretory phenotype regulation by dual drug delivery biomimetic nanoplatform for enhanced tumor chemotherapy |
| topic | MT: Regular Issue cancer-associated fibroblasts chemotherapy liposomes senescence-associated secretory phenotype tumor microenvironment |
| url | http://www.sciencedirect.com/science/article/pii/S2950329924000985 |
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