UTMD-Promoted Co-Delivery of Gemcitabine and miR-21 Inhibitor by Dendrimer-Entrapped Gold Nanoparticles for Pancreatic Cancer Therapy.
UTMD-Promoted Co-Delivery of Gemcitabine and miR-21 Inhibitor by Dendrimer-Entrapped Gold Nanoparticles for Pancreatic Cancer Therapy.
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UTMD 促进通过树枝状大分子包埋的金纳米颗粒共同递送吉西他滨和 miR-21 抑制剂用于胰腺癌治疗
作者：
Lin L;Fan Y;Gao F;Jin L;Li D;Sun W;Li F;Qin P;Shi Q;Shi X;Du L
传统的胰腺癌化疗存在药物渗透性低和固有或获得性耐药的问题。开发新的强化治疗策略仍然是一个巨大的挑战。本文中，我们报道了一种基于树突包裹金纳米颗粒（Au DENPs）的新型超声靶向微泡破坏（UTMD）促进递送系统，用于共同递送吉西他宾（Gem）和miR-21抑制剂（miR-21i）。方法：设计并合成Gem-Au DENPs/miR-21i。通过透射电子显微镜（TEM）、凝胶延迟实验和动态光散射（DLS）对所设计的复合物进行了表征。然后，在超声暴露平台上考察了最佳暴露参数。采用激光共聚焦显微镜、光谱微孔板阅读器、流式细胞仪和化学发光成像系统分析了其体外细胞摄取、细胞毒性和抗癌作用。最后，通过超声造影（CEUS）、苏木精伊红（H&E）染色、TUNEL染色及肿瘤体积比较评价其体内抗癌作用。结果：结果显示，gemu - au DENPs/miR-21i可被癌细胞摄取，且超声功率为0.4 W/cm2的UTMD可进一步促进细胞摄取，增强细胞通透性。此外，在UTMD治疗或不治疗的情况下，Gem和miR-21i共同递送的IC50值分别比自由Gem低82倍和13倍。通过体内治疗进一步验证了utmd促进Gem和miR-21i的共同递送，并显示异种移植胰腺肿瘤的肿瘤体积显着缩小，血液灌注增加。结论：UTMD技术可显著促进Au DENPs共同递送Gem和miR-21i，从而为有效治疗胰腺癌提供了一种有前景的策略。
Conventional chemotherapy of pancreatic cancer (PaCa) suffers the problems of low drug permeability and inherent or acquired drug resistance. Development of new strategies for enhanced therapy still remains a great challenge. Herein, we report a new ultrasound-targeted microbubble destruction (UTMD)-promoted delivery system based on dendrimer-entrapped gold nanoparticles (Au DENPs) for co-delivery of gemcitabine (Gem) and miR-21 inhibitor (miR-21i). Methods: In this study, Gem-Au DENPs/miR-21i was designed and synthesized. The designed polyplexes were characterized via transmission electron microscopy (TEM), Gel retardation assay and dynamic light scattering (DLS). Then, the optimum exposure parameters were examined by an ultrasound exposure platform. The cellular uptake, cytotoxicity and anticancer effects in vitro were analyzed by confocal laser microscopy, spectra microplate reader, flow cytometry and a chemiluminescence imaging system. Lastly, the anticancer effects in vivo were evaluated by contrast-enhanced ultrasound (CEUS), hematoxylin and eosin (H&E) staining, TUNEL staining and comparison of tumor volume. Results: The results showed that the Gem-Au DENPs/miR-21i can be uptake by cancer cells and the cellular uptake was further facilitated by UTMD with an ultrasound power of 0.4 W/cm2 to enhance the cell permeability. Further, the co-delivery of Gem and miR-21i with or without UTMD treatment displayed 82-fold and 13-fold lower IC50 values than the free Gem, respectively. The UTMD-promoted co-delivery of Gem and miR-21i was further validated by in vivo treatment and showed a significant tumor volume reduction and an increase in blood perfusion of xenografted pancreatic tumors. Conclusion: The co-delivery of Gem and miR-21i using Au DENPs can be significantly promoted by UTMD technology, hence providing a promising strategy for effective pancreatic cancer treatments.
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影响因子：
3.5
作者：
Aryal M;Park J;Vykhodtseva N;Zhang YZ;McDannold N
通讯作者：
McDannold N
DOI：
10.1002/wnan.1242
发表时间：
2014-01
影响因子：
8.6
作者：
Devulapally, Rammohan;Paulmurugan, Ramasamy
通讯作者：
Paulmurugan, Ramasamy
影响因子：
12.4
作者：
Ektate K;Kapoor A;Maples D;Tuysuzoglu A;VanOsdol J;Ramasami S;Ranjan A
通讯作者：
Ranjan A
影响因子：
9.5
作者：
Kong, Lingdan;Alves, Carla S.;Shi, Xiangyang
通讯作者：
Shi, Xiangyang
影响因子：
4.3
作者：
Ilic M;Ilic I
通讯作者：
Ilic I