αvβ3 integrin-specific exosomes engineered with cyclopeptide for targeted delivery of triptolide against malignant melanoma
Abstract Background Melanoma is the most malignant skin tumor and is difficult to cure with the alternative treatments of chemotherapy, biotherapy, and immunotherapy. Our previous study showed that triptolide (TP) exhibited powerful tumoricidal activity against melanoma. However, the clinical potent...
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| Format: | Article |
| Language: | English |
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BMC
2022-08-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-022-01597-1 |
| _version_ | 1817998917376147456 |
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| author | Yongwei Gu Yue Du Liangdi Jiang Xiaomeng Tang Aixue Li Yunan Zhao Yitian Lang Xiaoyan Liu Jiyong Liu |
| author_facet | Yongwei Gu Yue Du Liangdi Jiang Xiaomeng Tang Aixue Li Yunan Zhao Yitian Lang Xiaoyan Liu Jiyong Liu |
| author_sort | Yongwei Gu |
| collection | DOAJ |
| description | Abstract Background Melanoma is the most malignant skin tumor and is difficult to cure with the alternative treatments of chemotherapy, biotherapy, and immunotherapy. Our previous study showed that triptolide (TP) exhibited powerful tumoricidal activity against melanoma. However, the clinical potential of TP is plagued by its poor aqueous solubility, short half-life, and biotoxicity. Therefore, developing an ideal vehicle to efficiently load TP and achieving targeted delivery to melanoma is a prospective approach for making full use of its antitumor efficacy. Results We applied exosome (Exo) derived from human umbilical cord mesenchymal stromal cells (hUCMSCs) and engineered them exogenously with a cyclic peptide, arginine-glycine-aspartate (cRGD), to encapsulate TP to establish a bionic-targeted drug delivery system (cRGD-Exo/TP), achieving synergism and toxicity reduction. The average size of cRGD-Exo/TP was 157.34 ± 6.21 nm, with a high drug loading of 10.76 ± 1.21%. The in vitro antitumor results showed that the designed Exo delivery platform could be effectively taken up by targeted cells and performed significantly in antiproliferation, anti-invasion, and proapoptotic activities in A375 cells via the caspase cascade and mitochondrial pathways and cell cycle alteration. Furthermore, the biodistribution and pharmacokinetics results demonstrated that cRGD-Exo/TP possessed superior tumor targetability and prolonged the half-life of TP. Notably, cRGD-Exo/TP significantly inhibited tumor growth and extended survival time with negligible systemic toxicity in tumor-bearing mice. Conclusion The results indicated that the functionalized Exo platform provides a promising strategy for targeted therapy of malignant melanoma. Graphical Abstract |
| first_indexed | 2024-04-14T03:00:42Z |
| format | Article |
| id | doaj.art-cd5f332a89044aec86beac0dada6f370 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-14T03:00:42Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-cd5f332a89044aec86beac0dada6f3702022-12-22T02:15:55ZengBMCJournal of Nanobiotechnology1477-31552022-08-0120112010.1186/s12951-022-01597-1αvβ3 integrin-specific exosomes engineered with cyclopeptide for targeted delivery of triptolide against malignant melanomaYongwei Gu0Yue Du1Liangdi Jiang2Xiaomeng Tang3Aixue Li4Yunan Zhao5Yitian Lang6Xiaoyan Liu7Jiyong Liu8Department of Pharmacy, Fudan University Shanghai Cancer Center, Fudan UniversityDepartment of Pharmacy, Fudan University Shanghai Cancer Center, Fudan UniversityDepartment of Pharmacy, Fudan University Shanghai Cancer Center, Fudan UniversityDepartment of Pharmacy, Fudan University Shanghai Cancer Center, Fudan UniversityDepartment of Pharmacy, Fudan University Shanghai Cancer Center, Fudan UniversityDepartment of Pharmacy, Fudan University Shanghai Cancer Center, Fudan UniversityDepartment of Pharmacy, Huangpu Branch, Shanghai Ninth People‘s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Pharmacy, Huangpu Branch, Shanghai Ninth People‘s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Pharmacy, Fudan University Shanghai Cancer Center, Fudan UniversityAbstract Background Melanoma is the most malignant skin tumor and is difficult to cure with the alternative treatments of chemotherapy, biotherapy, and immunotherapy. Our previous study showed that triptolide (TP) exhibited powerful tumoricidal activity against melanoma. However, the clinical potential of TP is plagued by its poor aqueous solubility, short half-life, and biotoxicity. Therefore, developing an ideal vehicle to efficiently load TP and achieving targeted delivery to melanoma is a prospective approach for making full use of its antitumor efficacy. Results We applied exosome (Exo) derived from human umbilical cord mesenchymal stromal cells (hUCMSCs) and engineered them exogenously with a cyclic peptide, arginine-glycine-aspartate (cRGD), to encapsulate TP to establish a bionic-targeted drug delivery system (cRGD-Exo/TP), achieving synergism and toxicity reduction. The average size of cRGD-Exo/TP was 157.34 ± 6.21 nm, with a high drug loading of 10.76 ± 1.21%. The in vitro antitumor results showed that the designed Exo delivery platform could be effectively taken up by targeted cells and performed significantly in antiproliferation, anti-invasion, and proapoptotic activities in A375 cells via the caspase cascade and mitochondrial pathways and cell cycle alteration. Furthermore, the biodistribution and pharmacokinetics results demonstrated that cRGD-Exo/TP possessed superior tumor targetability and prolonged the half-life of TP. Notably, cRGD-Exo/TP significantly inhibited tumor growth and extended survival time with negligible systemic toxicity in tumor-bearing mice. Conclusion The results indicated that the functionalized Exo platform provides a promising strategy for targeted therapy of malignant melanoma. Graphical Abstracthttps://doi.org/10.1186/s12951-022-01597-1ExosomesTargeted deliverycRGDTriptolideMalignant melanoma |
| spellingShingle | Yongwei Gu Yue Du Liangdi Jiang Xiaomeng Tang Aixue Li Yunan Zhao Yitian Lang Xiaoyan Liu Jiyong Liu αvβ3 integrin-specific exosomes engineered with cyclopeptide for targeted delivery of triptolide against malignant melanoma Journal of Nanobiotechnology Exosomes Targeted delivery cRGD Triptolide Malignant melanoma |
| title | αvβ3 integrin-specific exosomes engineered with cyclopeptide for targeted delivery of triptolide against malignant melanoma |
| title_full | αvβ3 integrin-specific exosomes engineered with cyclopeptide for targeted delivery of triptolide against malignant melanoma |
| title_fullStr | αvβ3 integrin-specific exosomes engineered with cyclopeptide for targeted delivery of triptolide against malignant melanoma |
| title_full_unstemmed | αvβ3 integrin-specific exosomes engineered with cyclopeptide for targeted delivery of triptolide against malignant melanoma |
| title_short | αvβ3 integrin-specific exosomes engineered with cyclopeptide for targeted delivery of triptolide against malignant melanoma |
| title_sort | αvβ3 integrin specific exosomes engineered with cyclopeptide for targeted delivery of triptolide against malignant melanoma |
| topic | Exosomes Targeted delivery cRGD Triptolide Malignant melanoma |
| url | https://doi.org/10.1186/s12951-022-01597-1 |
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