Hyaluronic acid-functionalized polymeric nanoparticles for colon cancer-targeted combination chemotherapy.
Hyaluronic acid-functionalized polymeric nanoparticles for colon cancer-targeted combination chemotherapy.
复制标题
用于结肠癌靶向联合化疗的透明质酸功能化聚合物纳米颗粒
DOI：
10.1039/c5nr04831a
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发表时间：
2015-11-14
期刊：
影响因子：
6.7
通讯作者：
Merlin D
中科院分区：
文献类型：
--
作者：
Xiao B;Han MK;Viennois E;Wang L;Zhang M;Si X;Merlin D
基于纳米颗粒（NP）的联合化疗被认为是实现结肠癌治疗协同效应和靶向给药的有效策略。在这里，我们制备了一系列透明质酸（HA）功能化喜树碱(CPT)/姜黄素（CUR）负载的聚合物NPs (HA-CPT/CUR-NPs)， CPT与CUR的重量比分别为1:1,2:1和4:1。得到的球形HA-CPT/ cu - nps具有理想的粒径（约289 nm）、相对狭窄的粒径分布和略负的zeta电位。这些NPs在检查的整个时间框架内对两种药物表现出同时的缓释特征。随后的细胞摄取实验表明，与壳聚糖包被的NPs相比，将HA引入NP表面赋予NPs结肠癌靶向能力，并显著提高了NPs的细胞摄取效率。重要的是，在一个ha功能化的NP中联合递送CPT和CUR具有很强的协同效应。HA-CPT/CUR-NP（1:1）抗肿瘤活性最高，联合指数极低。总之，我们的研究结果表明，这种HA-CPT/CUR-NP可以作为结肠癌靶向联合化疗的有效配方。喜树碱和姜黄素已被共同负载到透明质酸功能化聚合物纳米颗粒（NPs）中。合成的NPs具有明显的结肠癌靶向给药能力，对结肠癌细胞具有较强的协同作用。
Nanoparticle (NP)-based combination chemotherapy has been proposed as an effective strategy for achieving synergistic effects and targeted drug delivery for colon cancer therapy. Here, we fabricated a series of hyaluronic acid (HA)-functionalized camptothecin (CPT)/curcumin (CUR)-loaded polymeric NPs (HA-CPT/CUR-NPs) with various weight ratios of CPT to CUR (1:1, 2:1 and 4:1). The resultant spherical HA-CPT/CUR-NPs had a desirable particle size (around 289 nm), relative narrow size distribution, and slightly negative zeta potential. These NPs exhibited a simultaneous sustained release profile for both drugs throughout the time frame examined. Subsequent cellular uptake experiments demonstrated that the introduction of HA to the NP surface endowed NPs with colon cancer-targeting capability and markedly increased cellular uptake efficiency compared with chitosan-coated NPs. Importantly, the combined delivery of CPT and CUR in one HA-functionalized NP exerted strong synergistic effects. HA-CPT/CUR-NP (1:1) showed the highest antitumor activity among the three HA-CPT/CUR-NPs, resulting in an extremely low combination index. Collectively, our findings indicate that this HA-CPT/CUR-NP can be exploited as an efficient formulation for colon cancer-targeted combination chemotherapy. Camptothecin and curcumin have been co-loaded into hyaluronic acid-functionalized polymeric nanoparticles (NPs). The resultant NPs exhibited obvious colon cancer-targeted drug delivery capability and strong synergistic effects against colon cancer cells.