Yang Muyang, Yu Lixia, Guo Ruiwei, Dong Anjie, Lin Cunguo, Zhang Jianhua
Department of Polymer Science and Technology, Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China.
Nanomaterials (Basel). 2018 Mar 15;8(3):167. doi: 10.3390/nano8030167.
Synergistic combination therapy by integrating chemotherapeutics and chemosensitizers into nanoparticles has demonstrated great potential to reduce side effects, overcome multidrug resistance (MDR), and thus improve therapeutic efficacy. However, with regard to the nanocarriers for multidrug codelivery, it remains a strong challenge to maintain design simplicity, while incorporating the desirable multifunctionalities, such as coloaded high payloads, targeted delivery, hemodynamic stability, and also to ensure low drug leakage before reaching the tumor site, but simultaneously the corelease of drugs in the same cancer cell. Herein, we developed a facile modular coassembly approach to construct an all-in-one multifunctional multidrug delivery system for the synergistic codelivery of doxorubicin (DOX, chemotherapeutic agent) and curcumin (CUR, MDR modulator). The acid-cleavable PEGylated polymeric prodrug (DOX--PCEC), tumor cell-specific targeting peptide (CRGDK-PEG-PCL), and natural chemosensitizer (CUR) were ratiometrically assembled into in one single nanocarrier (CUR/DOX--PCEC@CRGDK NPs). The resulting CUR/DOX--PCEC@CRGDK NPs exhibited several desirable characteristics, such as efficient and ratiometric drug loading, high hemodynamic stability and low drug leakage, tumor intracellular acid-triggered cleavage, and subsequent intracellular simultaneous drug corelease, which are expected to maximize a synergistic effect of chemotherapy and chemosensitization. Collectively, the multifunctional nanocarrier is feasible for the creation of a robust nanoplatform for targeted multidrug codelivery and efficient MDR modulation.
将化疗药物和化学增敏剂整合到纳米颗粒中进行协同联合治疗，已显示出在减少副作用、克服多药耐药性（MDR）以及提高治疗效果方面的巨大潜力。然而，对于用于多药共递送的纳米载体而言，在保持设计简单性的同时纳入所需的多功能特性（如高负载共载、靶向递送、血液动力学稳定性），并确保在到达肿瘤部位之前药物低泄漏，同时在同一癌细胞中实现药物的同时释放，仍然是一个巨大的挑战。在此，我们开发了一种简便的模块化共组装方法，以构建一种一体化的多功能多药递送系统，用于协同共递送阿霉素（DOX，化疗药物）和姜黄素（CUR，MDR调节剂）。将酸可裂解的聚乙二醇化聚合物前药（DOX--PCEC）、肿瘤细胞特异性靶向肽（CRGDK-PEG-PCL）和天然化学增敏剂（CUR）按比例组装到单个纳米载体（CUR/DOX--PCEC@CRGDK NPs）中。所得的CUR/DOX--PCEC@CRGDK NPs表现出几个理想的特性，如高效且按比例的药物负载、高血液动力学稳定性和低药物泄漏、肿瘤细胞内酸触发的裂解以及随后细胞内药物的同时释放，有望使化疗和化学增敏的协同效应最大化。总体而言，这种多功能纳米载体对于创建一个强大的纳米平台以实现靶向多药共递送和高效MDR调节是可行的。
