Tumor Cell-Derived Extracellular Vesicle-Coated Nanocarriers: An Efficient Theranostic Platform for the Cancer-Specific Delivery of Anti-miR-21 and Imaging Agents.
Tumor Cell-Derived Extracellular Vesicle-Coated Nanocarriers: An Efficient Theranostic Platform for the Cancer-Specific Delivery of Anti-miR-21 and Imaging Agents.
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DOI：
10.1021/acsnano.8b02587
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发表时间：
2018-11-27
期刊：
影响因子：
17.1
通讯作者：
Paulmurugan R
中科院分区：
文献类型：
--
作者：
Bose RJC;Uday Kumar S;Zeng Y;Afjei R;Robinson E;Lau K;Bermudez A;Habte F;Pitteri SJ;Sinclair R;Willmann JK;Massoud TF;Gambhir SS;Paulmurugan R
MicroRNAs是癌症发生、进展和传播的关键调控因子。大量证据表明，抑制过表达的致癌miRNA功能可能是一种强有力的抗癌治疗策略。然而，在体内靶向递送miRNA治疗各种类型的癌症仍然是一个主要的挑战。受其自然合成和货物递送能力的启发，研究人员利用肿瘤细胞衍生的细胞外囊泡（TEVs）用于癌症靶向递送治疗药物和治疗药物。在这里，我们研究了一个基于tev的纳米平台，用于多模态miRNA传递和光疗治疗以及癌症的磁共振成像。我们证明了anti-miR-21的负载可以阻断癌细胞中过表达的内源性致癌miR-21的功能，并随后由来自4T1细胞的tev递送。我们还从另外两种癌细胞系（HepG2和SKBR3）中制备了Cy5-anti-miR-21负载的tev，并证实了它们强大的同源和异源转染效率和细胞内Cy5-anti-miR-21传递。此外，tev介导的抗mir -21递送降低了乳腺癌细胞中的阿霉素（DOX）耐药性，其细胞杀伤效率比单独使用DOX处理的细胞高3倍。然后，我们研究了tev作为金氧化铁纳米颗粒（GIONs）功能化的仿生源，并在体外证明了TEV-GIONs的纳米治疗特性。TEV-GIONs在体外磁共振（MR）成像中表现出良好的T2对比，并在4T1细胞中产生有效的光热效应。我们还通过吲哚菁绿近红外染料标记，评估了anti-miR-21负载TEV-GIONs在体内的生物分布和治疗特性。我们使用磁共振成像进一步验证了tev区域的肿瘤特异性积累。我们的研究结果表明TEV-anti-miR-21-GIONs的分布模式与肿瘤靶向能力以及多柔比星联合治疗获得的活性和疗效密切相关。tev和tev - regions在未来的肿瘤分子成像和治疗中具有广阔的应用前景。
MicroRNAs are critical regulators of cancer initiation, progression, and dissemination. Extensive evidence suggests that the inhibition of over-expressed oncogenic miRNA function can be a robust strategy for anticancer therapy. However, in vivo targeted delivery of miRNA therapeutics to various types of cancers remains a major challenge. Inspired by their natural synthesis and cargo delivery capabilities, researchers have exploited tumor cell-derived extracellular vesicles (TEVs) for the cancer-targeted delivery of therapeutics and theranostics. Here, we investigate a TEV-based nanoplatform for multimodal miRNA delivery and phototherapy treatments as well as the magnetic resonance imaging of cancer. We demonstrated loading of anti-miR-21 that blocks the function of endogenous oncogenic miR-21 over-expressed in cancer cells into and subsequent delivery by TEVs derived from 4T1 cells. We also produced Cy5-anti-miR-21-loaded TEVs from two other cancer cell lines (HepG2 and SKBR3) and confirmed their robust homologous and heterologous transfection efficiency and intracellular Cy5-anti-miR-21 delivery. Additionally, TEV-mediated anti-miR-21 delivery attenuated doxorubicin (DOX) resistance in breast cancer cells with a 3-fold higher cell kill efficiency than in cells treated with DOX alone. We then investigated TEVs as a biomimetic source for the functionalization of gold-iron oxide nanoparticles (GIONs) and demonstrated nanotheranostic properties of TEV-GIONs in vitro. TEV-GIONs demonstrated excellent T2 contrast in in vitro magnetic resonance (MR) imaging and resulted in efficient photothermal effect in 4T1 cells. We also evaluated the biodistribution and theranostic property of anti-miR-21 loaded TEV-GIONs in vivo by labeling with indocyanine green near-infrared dye. We further validated the tumor specific accumulation of TEV-GIONs using MR imaging. Our findings demonstrate that the distribution pattern of the TEV-anti-miR-21-GIONs correlated well with the tumor-targeting capability as well as the activity and efficacy obtained in response to doxorubicin combination treatments. TEVs and TEV-GIONs are promising nanotheranostics for future applications in cancer molecular imaging and therapy.
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影响因子：
14
作者：
Fang RH;Jiang Y;Fang JC;Zhang L
通讯作者：
Zhang L
影响因子：
--
作者：
Gaudelot, Kelly;Gibier, Jean-Baptiste;Perrais, Michael
通讯作者：
Perrais, Michael
影响因子：
4.9
作者：
Ananta, Jeyarama S.;Paulmurugan, Ramasamy;Massoud, Tank F.
通讯作者：
Massoud, Tank F.
DOI：
10.1073/pnas.1418401112
发表时间：
2015-03-24
影响因子：
11.1
作者：
Kanada, Masamitsu;Bachmann, Michael H.;Contag, Christopher H.
通讯作者：
Contag, Christopher H.
肿瘤细胞来源的细胞外囊泡的治疗用途
DOI：
10.1007/978-1-4939-7253-1_35
发表时间：
2017-01-01
期刊：
EXTRACELLULAR VESICLES: METHODS AND PROTOCOLS
影响因子：
--
作者：
Liu, Jing;Ma, Jingwei;Huang, Bo
通讯作者：
Huang, Bo