Abstract

High intracellular reactive oxygen species (ROS) level is characteristic of cancer cells and could act as a target for the efficient targeted drug delivery for cancer treatment. Consequently, biomaterials that react to excessive levels of ROS are essential for biomedical applications. In this study, a novel ROS-responsive polymer based on D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) and poly (β-thioester) (TPGS-PBTE) was synthesized for targeted delivery of the first-line antineoplastic drug, paclitaxel (PTX). The resultant TPGS-PBTE NPs showed good ROS-responsive capability in size change and drug release. Compared to PTX, PTX-loaded nanoparticles (PTX@TPGS-PBTE NPs) showed enhanced cytotoxicity and higher level of apoptosis toward squamous cell carcinoma (SCC-7) cells. Tumor-targeted delivery of the NPs was also observed, especially after being modified with a tumor-targeting peptide, cRGD. Enhanced tumor growth inhibition was also observed in head and neck cancer SCC-7 murine models. In summary, PTX@TPGS-PBTE NPs can achieve good therapeutic effects of PTX against head and neck cancer both in vitro and in vivo, especially when modified by cRGD for active targeting, which enriched the application of ROS responsive system utilized in the delivery of anticancer drugs.

摘要

高细胞内活性氧 (ROS) 水平是癌细胞的特征，可以作为癌症治疗的有效靶向药物递送的靶标。因此，对过量 ROS 起反应的生物材料对于生物医学应用至关重要。在这项研究中，合成了一种基于 D-α-生育酚聚乙二醇 1000 琥珀酸酯 (TPGS) 和聚 (β-硫酯) (TPGS-PBTE) 的新型 ROS 响应聚合物，用于靶向递送一线抗肿瘤药物紫杉醇(PTX)。所得 TPGS-PBTE NPs 在尺寸变化和药物释放方面显示出良好的 ROS 响应能力。与 PTX 相比，负载 PTX 的纳米颗粒 (PTX@TPGS-PBTE NPs) 对鳞状细胞癌 (SCC-7) 细胞显示出增强的细胞毒性和更高水平的细胞凋亡。还观察到 NP 的肿瘤靶向递送，特别是在用肿瘤靶向肽 cRGD 修饰后。在头颈癌 SCC-7 小鼠模型中也观察到增强的肿瘤生长抑制。综上所述，PTX@TPGS-PBTE NPs在体外和体内均能达到PTX对头颈癌的良好治疗效果，尤其是当通过cRGD修饰进行主动靶向时，丰富了ROS反应系统在递送抗癌药。