Doxorubicin-Loaded Extracellular Vesicles Enhance Tumor Cell Death in Retinoblastoma.
Doxorubicin-Loaded Extracellular Vesicles Enhance Tumor Cell Death in Retinoblastoma.
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DOI：
10.3390/bioengineering9110671
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发表时间：
2022-11-10
影响因子：
4.6
通讯作者：
Ciolino, Joseph B.
中科院分区：
文献类型：
--
作者：
Farhat, Wissam;Yeung, Vincent;Kahale, Francesca;Parekh, Mohit;Cortinas, John;Chen, Lin;Ross, Amy E.;Ciolino, Joseph B.
化疗通常用于治疗视网膜母细胞瘤;然而，这种治疗方法具有严重的全身性不良反应和不足的治疗效果。细胞外囊泡（extracellular vesicles，EV）是重要的生物信息载体，在健康和病理条件下介导局部和全身细胞间的通讯。这些内源性囊泡已被确定为用于多种治疗有效载荷（包括多柔比星（Dox））的重要药物递送载体，具有优于传统技术的显著益处。在这项工作中，EV被用作天然药物递送纳米颗粒以负载Dox用于靶向递送到视网膜母细胞瘤人细胞系（Y-79）。从不同的乳腺癌细胞系（4 T1和SKBR 3）产生两种亚型的EV，所述乳腺癌细胞系表达选择性地与视网膜母细胞瘤细胞相互作用的标记物，并且利用细胞的内源性加载机制加载有Dox。在体外，我们观察到用两种EV递送Dox增加了细胞毒性，同时显著降低了药物的剂量。另一方面，装载Dox的EV通过激活caspase-3/7来抑制癌细胞生长。EV膜部分与视网膜母细胞瘤细胞表面受体的直接相互作用导致有效的药物递送至癌细胞。我们的研究结果强调了EV作为将Dox递送至视网膜母细胞瘤的最佳方法的有趣潜力。
Chemotherapy is often used to treat retinoblastoma; however, this treatment method has severe systemic adverse effects and inadequate therapeutic effectiveness. Extracellular vesicles (EVs) are important biological information carriers that mediate local and systemic cell-to-cell communication under healthy and pathological settings. These endogenous vesicles have been identified as important drug delivery vehicles for a variety of therapeutic payloads, including doxorubicin (Dox), with significant benefits over traditional techniques. In this work, EVs were employed as natural drug delivery nanoparticles to load Dox for targeted delivery to retinoblastoma human cell lines (Y-79). Two sub-types of EVs were produced from distinct breast cancer cell lines (4T1 and SKBR3) that express a marker that selectively interacts with retinoblastoma cells and were loaded with Dox, utilizing the cells’ endogenous loading machinery. In vitro, we observed that delivering Dox with both EVs increased cytotoxicity while dramatically lowering the dosage of the drug. Dox-loaded EVs, on the other hand, inhibited cancer cell growth by activating caspase-3/7. Direct interaction of EV membrane moieties with retinoblastoma cell surface receptors resulted in an effective drug delivery to cancer cells. Our findings emphasize the intriguing potential of EVs as optimum methods for delivering Dox to retinoblastoma.
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DOI：
10.1111/tra.12803
发表时间：
2021-07
期刊：
Traffic (Copenhagen, Denmark)
影响因子：
--
作者：
Donoso-Quezada J;Ayala-Mar S;González-Valdez J
通讯作者：
González-Valdez J
影响因子：
168.9
作者：
Dimaras, Helen;Kimani, Kahaki;Gallie, Brenda L.
通讯作者：
Gallie, Brenda L.
影响因子：
4.6
作者：
Aiello S;Rocchetta F;Longaretti L;Faravelli S;Todeschini M;Cassis L;Pezzuto F;Tomasoni S;Azzollini N;Mister M;Mele C;Conti S;Breno M;Remuzzi G;Noris M;Benigni A
通讯作者：
Benigni A
影响因子：
3.7
作者：
Akagi T;Kato K;Kobayashi M;Kosaka N;Ochiya T;Ichiki T
通讯作者：
Ichiki T
影响因子：
13.7
作者：
Abramson, David H.;Dunkel, Ira J.;Gobin, Y. Pierre
通讯作者：
Gobin, Y. Pierre