Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University , Hsinchu, Taiwan ROC.
ACS Appl Mater Interfaces. 2014 Dec 24;6(24):21832-41. doi: 10.1021/am5026243. Epub 2014 Jun 20.
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)3 sequence 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 TMPyP4 molecules 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.
各种平台被开发为创新的纳米载体，将治疗剂递送到病变部位。多功能表面修饰允许药物载体被靶向细胞更增强识别和摄取。然而，一些肿瘤细胞中的药物耐药性的发展在化疗失败中起着主要作用。联合使用的药物，称为多药物递送方法，旨在提高治疗效果，已成为一种越来越被广泛应用的策略，在临床癌症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）被用作纳米平台，共递两种不同的抗癌药物，以提高药物效果。Au NPs（直径 13nm）的表面与 AS1411 适配体组装，其与接近 Au NPs 的 21 个碱基对的（CGATCGA）3 序列连接。光敏剂 5,10,15,20-四（1-甲基吡啶-4-基）卟啉（TMPyP4）和化疗药物阿霉素（Dox）随后被物理连接到 AS1411 缀合的 Au NPs（T/D：ds-NPs）上，并递送到靶肿瘤细胞，如 HeLa 和 Dox 耐药 MCF-7R 细胞系。当暴露于 632nm 光时，TMPyP4 分子在活细胞内产生的活性氧物质引发细胞损伤。此外，在光动力反应过程中，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。总之，成功建立了共药物递送平台，以提高肿瘤细胞的治疗效果。光动力刺激触发释放的改善得到增强，从而在靶向药物递送中实现了高度有前途的精确药物释放。
