Aptamer-Functionalized Gold Nanoparticles As Photoresponsive Nanoplatform for Co-Drug Delivery
Aptamer-Functionalized Gold Nanoparticles As Photoresponsive Nanoplatform for Co-Drug Delivery
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DOI：
10.1021/am5026243
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发表时间：
2014-12-24
影响因子：
9.5
通讯作者：
Huang, Yu-Fen
中科院分区：
文献类型：
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作者：
Shiao, Yi-Syun;Chiu, Huai-Hsuan;Huang, Yu-Fen
已经开发了各种平台作为创新的纳米载体，以将治疗剂递送到患病部位。多功能表面修饰允许靶向细胞增强对药物载体的识别和摄取。然而，在某些肿瘤细胞中产生耐药性是化疗失败的主要原因。多药联合给药是提高肿瘤治疗效果的一种有效方法，在临床肿瘤治疗中具有重要意义。在这项研究中，适配子功能化的金纳米粒子（Au NPs）已被用作纳米平台，以共同提供两种不同的抗癌药物，以提高药物的有效性。在直径为13 nm的Au NPs表面组装AS 1411适配体，AS 1411适配体与靠近Au NPs的21个碱基对的（CGATCGA）3序列相连。然后将光敏剂5，10，15，20-四（1-甲基吡啶-4-基）卟啉（TMPyP 4）和化疗药物阿霉素（Dox）物理连接到AS 1411缀合的Au NP（T/D：ds-NP）上，并递送到靶肿瘤细胞，如HeLa和Dox抗性MCF-7 R细胞系。当暴露于632 nm光时，由TMPyP 4分子诱导的活性氧在活细胞内产生，随后细胞损伤。此外，在光动力学反应过程中，互补药物的触发释放也同时发生。在Dox分子存在下，对靶细胞的毒性优于单独药物治疗的上级。总体而言，成功建立了联合药物递送平台，以提高在肿瘤细胞中的治疗效果。光动力刺激触发释放的改善得到加强，因此在靶向药物递送中具有很高的应用前景。
Various platforms have been developed as innovative nanocarriers to deliver therapeutic agents to the diseased sites. Multifunctional surface modification allows an enhanced recognition and uptake of drug carriers by targeted cells. However, the development of drug resistance in some tumor cells plays a major role in the failure of chemotherapy. Drugs given in combination, called multidrug delivery approach, was designed to improve the therapeutic efficacy and has become an increasingly used strategy that is of great importance in clinical cancer treatments. In this study, aptamer-functionalized gold nanoparticles (Au NPs) have been used as a nanoplatform to codeliver two different anticancer drugs for improving the drug effectiveness. The surface of Au NPs (13 nm in diameter) was assembled with AS1411 aptamers, which tethered with 21-base pairs of (CGATCGA)3sequence approached to the Au NPs. Both the photosensitizer 5,10,15,20-tetrakis(1-methylpyridinium-4-yl) porphyrin (TMPyP4) and the chemotherapeutic drug doxorubicin (Dox) were then physically attached to the AS1411-conjugated Au NPs (T/D:ds-NPs) and delivered to the target tumor cells such as HeLa and Dox-resistant MCF-7R cell lines. When exposed to a 632 nm light, reactive oxygen species induced by TMPyP4molecules were generated inside the living cells, followed by cell damage. In addition, triggered release of the complementary drugs also occurred simultaneously during the photodynamic reaction. In the presence of Dox molecules, the toxicity toward the target cells was superior to individual drug treatment. Overall, a co-drug delivery platform was successfully established to improve the therapeutic efficacy in tumor cells. The improvement of the photodynamic-stimulated triggered release was enhanced, thus highly promising precise drug release in targeted drug delivery.