Department of Bioengineering and Biotechnology, College of Chemical Engineering, Huaqiao University, Xiamen, Fujian, 361021, China.
Department of Bioengineering and Biotechnology, College of Chemical Engineering, Huaqiao University, Xiamen, Fujian, 361021, China.
Eur J Pharmacol. 2021 Mar 5;894:173814. doi: 10.1016/j.ejphar.2020.173814. Epub 2020 Dec 19.
Pancreatic cancer is a high degree malignant tumor which makes its diagnosis and treatment highly critical. The effect of conventional chemotherapy for pancreatic cancer is quite poor due to the low accumulation of the chemotherapeutic drugs at the tumor site. Therefore, enhancing the targeting efficiency and accumulation of the drug carrier at tumor site with subsequent release of drug within the effective time period is one of the key factors for successful targeted chemotherapy of pancreatic cancer. Our previous studies have demonstrated that aptamer can be a valid targeting moiety to guide the chemotherapeutic drug doxorubicin (DOX) to accumulate at the tumor tissue. Herein, the present study aims to further investigate the targeting efficiency as well as therapeutic efficacy of the drug delivery system comprised of aptamer-modified polymeric nano drug carrier encapsulated with DOX (DOX@PCL-b-PEO-Aptamer micelles). The in vitro cytotoxicity studies and laser confocal microscopy indicated that DOX@PCL-b-PEO-Aptamer micelles exhibited enhanced targeting and cytotoxic efficacy towards human pancreatic cancer cells (Panc-1 cells) as compared to free DOX and DOX-loaded PCL-b-PEO-NH micelles (DOX@PCL-b-PEO-NH micelles). Furthermore, the aptamer-decorated drug delivery system exhibited better tumor penetration into the three-dimensional (3D) spheroid of Panc-1 cells with successful release of DOX as compared to the drug delivery system without aptamer modification. Overall, this study suggests that the aptamer-modified polymeric micelles could be effectively employed for the targeted delivery of anticancer drug to treat pancreatic cancer in near future.
胰腺癌是一种高度恶性肿瘤，其诊断和治疗极具挑战性。由于化疗药物在肿瘤部位的积累量低，常规化疗治疗胰腺癌的效果相当差。因此，提高药物载体在肿瘤部位的靶向效率和积累量，并在有效时间内释放药物，是胰腺癌成功靶向化疗的关键因素之一。我们之前的研究表明，适体可以作为一种有效的靶向部分，引导多柔比星（DOX）等化疗药物聚集在肿瘤组织中。在此，本研究旨在进一步研究由适体修饰的载有多柔比星（DOX@PCL-b-PEO-Aptamer 胶束）的聚合物纳米药物载体的靶向效率和治疗效果。体外细胞毒性研究和激光共聚焦显微镜表明，与游离 DOX 和载 DOX 的 PCL-b-PEO-NH 胶束（DOX@PCL-b-PEO-NH 胶束）相比，DOX@PCL-b-PEO-Aptamer 胶束对人胰腺癌细胞（Panc-1 细胞）具有增强的靶向和细胞毒性作用。此外，与未修饰适体的药物递送系统相比，修饰适体的药物递送系统能够更好地穿透三维（3D）Panc-1 细胞球体并成功释放 DOX。总的来说，这项研究表明，适体修饰的聚合物胶束可有效用于未来靶向递送抗癌药物治疗胰腺癌。
