Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, People's Republic of China.
Department of Pharmacy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, People's Republic of China.
Int J Nanomedicine. 2019 May 15;14:3557-3569. doi: 10.2147/IJN.S198511. eCollection 2019.
Combining siRNA and other chemotherapeutic agents into one nanocarrier can overcome the multidrug resistance (MDR) phenomenon by synergistically MDR relative genes silencing and elevated chemotherapeutic activity. Most of these systems are typically fabricated through complicated procedures, which involves materials preparation, drug loading and modifications. Herein, the purpose of this study is to develop a new and fast co-delivery system of siRNA and doxorubicin for potentially synergistic cancer treatment. The co-delivery system is constructed conveniently by a stable complex consisting of doxorubicin bound to siRNA via intercalation firstly, followed by interacting with (3-Aminopropyl)triethoxysilane (APTES) electrostatically and Tetraethyl orthosilicate (TEOS) co-condensed, and the characterizations of the resultant nanocarrier are also investigated. Furthermore, this study evaluates the synergistic anti-cancer efficacy in MCF-7/MDR cells after treatment of siRNA and doxorubicin 'two in one' nanocarriers. We establish a new and fast method to craft a co-delivery system of siRNA and doxorubicin with controllable and nearly uniform size, and the entire fabrication process only costs in about 10 minutes. The resultant co-delivery system presents high loading capacities of siRNA and doxorubicin, and the encapsulated doxorubicin plays a pH-responsive control release. Further, biological functionality tests of the synthesized co-delivery nanocarriers show high inhibition of P-gp protein encoded by MDR-1 gene in MCF-7/MDR cells (a variant of human breast cancer cell line with drug resistance) after transfection of these nanocarriers carrying MDR-1 siRNA and doxorubicin simultaneously, which sensitize the MCF-7/MDR cells to doxorubicin, overall leading to improved cell suppression. Collectively, this co-delivery system not only serves as potent therapeutics for synergistic cancer therapy, it also may facilitate the bench-to-bedside translation of combinatorial delivery system as a robust drug nanocarrier by allowing for fabricating a simply and fast nanocarrier for co-delivery of siRNA and doxorubicin with predictable high production rate.
将 siRNA 和其他化疗药物结合到一个纳米载体中，可以通过协同沉默多药耐药（MDR）相关基因和提高化疗药物活性来克服多药耐药（MDR）现象。这些系统中的大多数通常是通过复杂的程序来制造的，包括材料的制备、药物的负载和修饰。在此，本研究旨在开发一种新的、快速的 siRNA 和阿霉素协同递药系统用于潜在的协同癌症治疗。该共递药系统通过首先将阿霉素与 siRNA 结合形成稳定的复合物，然后通过静电相互作用与（3-氨丙基）三乙氧基硅烷（APTES）相互作用，以及四乙氧基硅烷（TEOS）共缩合来构建，还对所得纳米载体的特性进行了研究。此外，本研究还评估了 MCF-7/MDR 细胞经 siRNA 和阿霉素“双管齐下”纳米载体处理后的协同抗癌疗效。我们建立了一种新的、快速的方法来制备具有可控且几乎均匀尺寸的 siRNA 和阿霉素共递药系统，整个制备过程仅需约 10 分钟。所得共递药系统具有高载药量的 siRNA 和阿霉素，封装的阿霉素具有 pH 响应性控制释放。此外，合成的共递药纳米载体的生物学功能测试表明，这些同时携带 MDR-1 siRNA 和阿霉素的纳米载体转染 MCF-7/MDR 细胞后，对多药耐药基因（MDR-1 基因）编码的 P-糖蛋白（P-gp）具有高抑制作用，使 MCF-7/MDR 细胞对阿霉素敏感，从而提高细胞抑制率。总的来说，该共递药系统不仅为协同癌症治疗提供了有效的治疗方法，还可能通过允许制备简单快速的纳米载体来促进组合递药系统的从实验室到临床的转化，作为一种强大的药物纳米载体，以可预测的高生产率同时递送 siRNA 和阿霉素。
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