Xiao Bo, Si Xiaoying, Han Moon Kwon, Viennois Emilie, Zhang Mingzhen, Merlin Didier
Institute for Clean Energy and Advanced Materials, Faculty for Materials and Energy, Southwest University, Chongqing, 400715, P. R. China ; Center for Diagnostics and Therapeutics, Institute for Biomedical Science, Georgia State University, Atlanta, 30302, USA.
Institute for Clean Energy and Advanced Materials, Faculty for Materials and Energy, Southwest University, Chongqing, 400715, P. R. China.
J Mater Chem B. 2015 Oct 21;3(39):7724-7733. doi: 10.1039/c5tb01245g. Epub 2015 Sep 1.
Nanoparticle (NP)-based combination chemotherapy has been proposed as a potent strategy for enhancing intracellular drug concentrations and achieving synergistic effects in colon cancer therapy. Here, we fabricated a series of chitosan-functionalized camptothecin (CPT)/curcumin (CUR)-loaded polymeric NPs with various weight ratios of CPT to CUR. The resultant cationic spherical CPT/CUR-NPs had a desirable particle size (193-224 nm), relatively narrow size distribution, and slightly positive zeta-potential. These NPs exhibited a simultaneous sustained release profile for both drugs throughout the study period with a slight, initial burst release. Subsequent cellular uptake experiments demonstrated that the introduction of chitosan to the NP surface markedly increased cellular-uptake efficiency compared with other drug formulations, and thus increased the intracellular drug concentrations. Importantly, the combined delivery of CPT and CUR in a single NP enhanced synergistic effects of the two drugs. Among the five cationic CPT/CUR-NPs tested, NPs with a CPT/CUR weight ratio of 4:1 showed the highest anticancer activity, resulting in a combination index of approximately 0.46. In summary, our study represents the first report of combinational application of CPT and CUR with a one-step-fabricated co-delivery system for effective colon cancer combination chemotherapy.
基于纳米颗粒（NP）的联合化疗已被提出作为一种有效的策略，用于提高细胞内药物浓度并在结肠癌治疗中实现协同效应。在此，我们制备了一系列载有不同重量比喜树碱（CPT）/姜黄素（CUR）的壳聚糖功能化聚合物纳米颗粒。所得的阳离子球形CPT/CUR-NPs具有理想的粒径（193-224nm）、相对较窄的粒径分布和略微正的zeta电位。在整个研究期间，这些纳米颗粒对两种药物均呈现出同时持续释放的特性，伴有轻微的初始突发释放。随后的细胞摄取实验表明，与其他药物制剂相比，在纳米颗粒表面引入壳聚糖显著提高了细胞摄取效率，从而增加了细胞内药物浓度。重要的是，在单个纳米颗粒中联合递送CPT和CUR增强了两种药物的协同效应。在所测试的五种阳离子CPT/CUR-NPs中，CPT/CUR重量比为4:1的纳米颗粒显示出最高的抗癌活性，联合指数约为0.46。总之，我们的研究首次报道了CPT和CUR通过一步制备的共递送系统联合应用于有效的结肠癌联合化疗。
