Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, and Shanghai Minimally Invasive Surgery Center, Shanghai, 200025, P. R. China.
J Mater Chem B. 2019 Jan 21;7(3):433-442. doi: 10.1039/c8tb02574f. Epub 2018 Dec 19.
Platinum (Pt)-based drugs including cisplatin, carboplatin and oxaliplatin have been widely used as first-line anticancer regimens due to their excellent anticancer efficacy. However, the clinical application of these drugs is greatly limited due to their side effects and drug resistance. In this study, an antitumor drug delivery system based on carboplatin prodrug loading FeO nanoparticles (NPs@carboplatin) was developed and the antitumor activity was also investigated. The as-synthesized NPs@carboplatin has an average diameter of 7.88 nm with a zeta potential of 8.11 mV. It exhibited a higher cytotoxic effect than carboplatin on both A2780 (cisplatin sensitive) and A2780DDP (cisplatin resistant) ovarian cancer cells via MTT assay, which can overcome Pt resistance. Moreover, the nanoparticles (NPs) loaded with carboplatin possess excellent delivery capability, which can be effectively taken up by ovarian cancer cell lines through an endocytosis process. With excellent delivery capability as carriers, NPs@carboplatin can promote drug internalization and result in the increase of intracellular drug accumulation with enhanced cellular cytotoxicity. Furthermore, in vivo experiments demonstrated that NPs@carboplatin can be widely distributed into major organs, and in the presence of an external magnetic field, the FeO nanocarrier is beneficial to visualize the tumor site location and promote the subsequent antitumor efficacy. It revealed a relatively high tumor inhibition rate without obvious potential toxicity to normal organs. Taken together, these results indicate that the magnetically targeted NPs@carboplatin can act as a drug delivery system and will have great potential in ovarian cancer therapeutic applications.
铂类药物（包括顺铂、卡铂和奥沙利铂）因其优异的抗癌疗效而被广泛用作一线抗癌药物。然而，由于其副作用和耐药性，这些药物的临床应用受到了极大的限制。在本研究中，开发了一种基于卡铂前药负载 FeO 纳米粒子（NPs@carboplatin）的抗肿瘤药物输送系统，并研究了其抗肿瘤活性。所合成的 NPs@carboplatin 的平均直径为 7.88nm，zeta 电位为 8.11mV。通过 MTT 测定，它对 A2780（顺铂敏感）和 A2780DDP（顺铂耐药）卵巢癌细胞的细胞毒性作用均高于卡铂，从而克服了铂耐药性。此外，负载卡铂的纳米粒子（NPs）具有优异的递药能力，能够通过内吞作用被卵巢癌细胞系有效摄取。作为具有优异递药能力的载体，NPs@carboplatin 可以促进药物内化，增加细胞内药物积累，增强细胞毒性。此外，体内实验表明，NPs@carboplatin 可以广泛分布到主要器官中，在外加磁场的作用下，FeO 纳米载体有利于可视化肿瘤部位并促进随后的抗肿瘤疗效。它表现出相对较高的肿瘤抑制率，对正常器官没有明显的潜在毒性。综上所述，这些结果表明，磁性靶向 NPs@carboplatin 可以作为一种药物输送系统，在卵巢癌治疗应用中具有巨大的潜力。
