Co-delivery of camptothecin and curcumin by cationic polymeric nanoparticles for synergistic colon cancer combination chemotherapy.
Co-delivery of camptothecin and curcumin by cationic polymeric nanoparticles for synergistic colon cancer combination chemotherapy.
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阳离子聚合物纳米颗粒共同递送喜树碱和姜黄素用于协同结肠癌联合化疗
DOI：
10.1039/c5tb01245g
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发表时间：
2015-10-21
期刊：
影响因子：
--
通讯作者：
Merlin D
中科院分区：
文献类型：
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作者：
Xiao B;Si X;Han MK;Viennois E;Zhang M;Merlin D
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。在这里，我们制造了一系列壳聚糖官能化的喜树碱（CPT）/姜黄素（CUR）负载的聚合物纳米粒子与各种重量比的CPT到CUR。所得阳离子球形CPT/CUR-NP具有所需的粒度（193-224 nm）、相对窄的粒度分布和稍微正的ζ-电位。这些NP在整个研究期间表现出两种药物的同时持续释放曲线，具有轻微的初始突释。随后的细胞摄取实验表明，与其他药物制剂相比，将壳聚糖引入NP表面显著增加了细胞摄取效率，从而增加了细胞内药物浓度。重要的是，CPT和CUR在单个NP中的组合递送增强了两种药物的协同作用。在测试的五种阳离子CPT/CUR-NP中，CPT/CUR重量比为4：1的NP显示出最高的抗癌活性，导致约0.46的组合指数。总之，我们的研究代表了CPT和CUR与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的第一份报告。
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.