Huang Yanyu, He Lizhen, Song Zhenhuan, Chan Leung, He Jintao, Huang Wei, Zhou Binwei, Chen Tianfeng
Department of Chemistry, Jinan University, Guangzhou 510632, China.
J Mater Chem B. 2017 May 14;5(18):3300-3314. doi: 10.1039/c7tb00287d. Epub 2017 Apr 24.
Resistance to chemotherapy remains the primary obstacle for the successful treatment of cancers. Nanotechnology-based studies have developed many smart nanomedicines and efficient strategies to overcome multidrug resistance (MDR), which have brought new horizons to cancer therapy. Among them, protein-based nanomedicine represents an appealing drug delivery platform to realize safe and superior therapeutic effects due to its paramount biocompatibility with minimized toxicity. Herein we describe the rational design and construction of a novel protein-based nanocarrier using the naturally-occurring protein phycocyanin (PC) as the base material, to achieve safe and tumor-specific drug delivery. This cancer-targeting nanosystem (FA-PCNP@DOX) with bio-responsive properties exhibits positive targeting accumulation in resistant cancer cells and overcomes drug efflux by enhancing cellular uptake and retention time. Specifically, FA-PCNP@DOX inhibits the function of pumping proteins of the ABC family and triggers ROS-mediated apoptotic signaling pathways, thereby attaining highly efficient anticancer efficacy and overcoming drug resistance. Pharmaceutical studies demonstrate that FA-PCNP@DOX overwhelms DOX by sustained release in the blood, which verifies its prolonged circulation in vivo. Moreover, FA-PCNP@DOX efficiently accumulates in tumors and strengthens the tumor inhibitory effect of DOX by enhanced tumoral penetration. Importantly, FA-PCNP@DOX effectively reduces the hepatic, pulmonary, renal and cardiac toxicity caused by DOX. Therefore, as a new nanocarrier, this novel nanosystem could be further exploited as a safe and versatile nanoplatform for next-generation cancer therapy.
化疗耐药性仍然是癌症成功治疗的主要障碍。基于纳米技术的研究已经开发出许多智能纳米药物和有效策略来克服多药耐药性（MDR），为癌症治疗带来了新的前景。其中，基于蛋白质的纳米药物由于其极高的生物相容性和最小的毒性，代表了一个有吸引力的药物递送平台，可实现安全且卓越的治疗效果。在此，我们描述了一种新型基于蛋白质的纳米载体的合理设计与构建，该载体以天然存在的蛋白质藻蓝蛋白（PC）为基础材料，以实现安全且肿瘤特异性的药物递送。这种具有生物响应特性的癌症靶向纳米系统（FA-PCNP@DOX）在耐药癌细胞中表现出阳性靶向积累，并通过增强细胞摄取和保留时间来克服药物外排。具体而言，FA-PCNP@DOX抑制ABC家族转运蛋白的功能并触发ROS介导的凋亡信号通路，从而获得高效的抗癌疗效并克服耐药性。药学研究表明，FA-PCNP@DOX在血液中通过持续释放超过阿霉素（DOX），这证实了其在体内的延长循环。此外，FA-PCNP@DOX有效地在肿瘤中积累，并通过增强肿瘤渗透增强DOX的肿瘤抑制作用。重要的是，FA-PCNP@DOX有效降低了DOX引起的肝、肺、肾和心脏毒性。因此，作为一种新型纳米载体，这种新型纳米系统可进一步开发成为下一代癌症治疗的安全且通用的纳米平台。
