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αvβ3 integrin-specific exosomes engineered with cyclopeptide for targeted delivery of triptolide against malignant melanoma
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 T...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9400227/ https://www.ncbi.nlm.nih.gov/pubmed/35999612 http://dx.doi.org/10.1186/s12951-022-01597-1 |
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author | Gu, Yongwei Du, Yue Jiang, Liangdi Tang, Xiaomeng Li, Aixue Zhao, Yunan Lang, Yitian Liu, Xiaoyan Liu, Jiyong |
author_facet | Gu, Yongwei Du, Yue Jiang, Liangdi Tang, Xiaomeng Li, Aixue Zhao, Yunan Lang, Yitian Liu, Xiaoyan Liu, Jiyong |
author_sort | Gu, Yongwei |
collection | PubMed |
description | 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: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-022-01597-1. |
format | Online Article Text |
id | pubmed-9400227 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-94002272022-08-25 αvβ3 integrin-specific exosomes engineered with cyclopeptide for targeted delivery of triptolide against malignant melanoma Gu, Yongwei Du, Yue Jiang, Liangdi Tang, Xiaomeng Li, Aixue Zhao, Yunan Lang, Yitian Liu, Xiaoyan Liu, Jiyong J Nanobiotechnology Research 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: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-022-01597-1. BioMed Central 2022-08-23 /pmc/articles/PMC9400227/ /pubmed/35999612 http://dx.doi.org/10.1186/s12951-022-01597-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Gu, Yongwei Du, Yue Jiang, Liangdi Tang, Xiaomeng Li, Aixue Zhao, Yunan Lang, Yitian Liu, Xiaoyan Liu, Jiyong αvβ3 integrin-specific exosomes engineered with cyclopeptide for targeted delivery of triptolide against 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 | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9400227/ https://www.ncbi.nlm.nih.gov/pubmed/35999612 http://dx.doi.org/10.1186/s12951-022-01597-1 |
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