αvβ3 integrin-specific exosomes engineered with cyclopeptide for targeted delivery of triptolide against malignant melanoma.
αvβ3 integrin-specific exosomes engineered with cyclopeptide for targeted delivery of triptolide against malignant melanoma.
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DOI：
10.1186/s12951-022-01597-1
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发表时间：
2022-08-23
影响因子：
10.2
通讯作者：
Liu, Jiyong
中科院分区：
文献类型：
--
作者：
Gu, Yongwei;Du, Yue;Jiang, Liangdi;Tang, Xiaomeng;Li, Aixue;Zhao, Yunan;Lang, Yitian;Liu, Xiaoyan;Liu, Jiyong
黑色素瘤是最恶性的皮肤肿瘤，并且难以用化学疗法、生物疗法和免疫疗法的替代疗法治愈。我们的前期研究表明雷公藤内酯醇（TP）对黑色素瘤具有很强的杀瘤活性。然而，TP的临床潜力受到其水溶性差、半衰期短和生物毒性的困扰。因此，开发一种理想的载体来有效地负载TP并实现对黑色素瘤的靶向递送是充分利用其抗肿瘤功效的一种有前景的方法。本研究应用人脐带间充质基质细胞（human umbilical cord mesenchymal stromal cells，hUCMSCs）的外泌体（exosome，Exo），并将其与环肽精氨酸-甘氨酸-天冬氨酸（cRGD）进行外源性基因修饰，构建了一种生物靶向给药系统（cRGD-Exo/TP），实现了协同减毒作用。cRGD-Exo/TP的平均粒径为157.34 ± 6.21 nm，载药量为10.76 ± 1.21%。体外抗肿瘤实验结果表明，所设计的Exo载体能够被靶细胞有效摄取，并通过caspase级联反应、线粒体途径和细胞周期改变等途径，对A375细胞具有明显的抗增殖、抗侵袭和促凋亡作用。此外，生物分布和药代动力学结果表明，cRGD-Exo/TP具有上级的肿瘤靶向性，并延长了TP的半衰期。值得注意的是，cRGD-Exo/TP在荷瘤小鼠中显著抑制肿瘤生长并延长存活时间，全身毒性可忽略不计。结果表明，功能化的Exo平台为恶性黑色素瘤的靶向治疗提供了一个有前途的策略。在线版本包含补充材料，可通过10.1186/s12951-022-01597-1获得。
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. 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. The results indicated that the functionalized Exo platform provides a promising strategy for targeted therapy of malignant melanoma. The online version contains supplementary material available at 10.1186/s12951-022-01597-1.
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DOI：
10.1093/brain/awab113
发表时间：
2021-07-28
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Akin EJ;Alsaloum M;Higerd GP;Liu S;Zhao P;Dib-Hajj FB;Waxman SG;Dib-Hajj SD
通讯作者：
Dib-Hajj SD
巨噬细胞-癌症混合膜包被纳米粒子用于乳腺癌治疗中的肺转移靶向
影响因子：
10.2
作者：
Gong, Chunai;Yu, Xiaoyan;Yuan, Yongfang
通讯作者：
Yuan, Yongfang
影响因子：
10.2
作者：
Guo Y;Wan Z;Zhao P;Wei M;Liu Y;Bu T;Sun W;Li Z;Yuan L
通讯作者：
Yuan L
影响因子：
10
作者：
Evers, Martijn J. W.;van de Wakker, Simonides, I;Vader, Pieter
通讯作者：
Vader, Pieter
影响因子：
4.9
作者：
Bannunah, Azzah M.;Vllasaliu, Driton;Stolnik, Snjezana
通讯作者：
Stolnik, Snjezana