Nanoparticles are attractive platforms for the delivery of various anticancer therapeutics. Nevertheless, their applications are still limited by the relatively low drug loading capacity and the occurrence of multidrug resistance (MDR) against chemotherapeutics. In this study, we report that the integration of d-α-tocopherol succinate (VES) residue with both chitosan and paclitaxel (PTX) led to significant improvement of drug loading capacity and drug loading efficiency through the enhancement of drug/carrier interaction. After the incorporation of hyaluronic acid containing PEG side chains (HA-PEG), higher serum stability and more efficient cellular uptake were obtained. Due to HA coating, VES residues and the enzymatic responsive drug release property, such facile nanoparticles actively targeted cancer cells that overexpress CD44 receptor and efficiently reversed the MDR of treated cells, but caused no significant toxicity to mouse fibroblast (NIH-3T3). More importantly, with HA-PEG coating, longer blood circulation and more effective tumor accumulation were achieved for prodrug nanoparticles. Finally, superior anticancer activity and excellent safety profile was demonstrated by HA-PEG coated enzymatically activatable prodrug nanoparticles compared to commercially available Taxol formulation.

中文翻译：

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CD44靶向的酶促可活化壳聚糖纳米粒子的有效抗肿瘤治疗和多药耐药性的逆转。

纳米颗粒是用于递送各种抗癌治疗剂的有吸引力的平台。然而，它们的应用仍然受到相对较低的药物装载能力和对化学疗法的多重耐药性（MDR）的出现的限制。在这项研究中，我们报告了d的积分带有壳聚糖和紫杉醇（PTX）的-α-生育酚琥珀酸酯（VES）残留物通过增强药物/载体相互作用，显着改善了药物载量和载药效率。掺入含有PEG侧链的透明质酸（HA-PEG）后，可获得更高的血清稳定性和更有效的细胞摄取。由于具有HA涂层，VES残基和酶促响应药物释放特性，此类轻巧的纳米粒子主动靶向了过表达CD44受体并有效逆转治疗细胞的MDR的癌细胞，但对小鼠成纤维细胞（NIH-3T3）没有明显的毒性。更重要的是，通过HA-PEG涂层，前药纳米颗粒可实现更长的血液循环和更有效的肿瘤蓄积。最后，