本研究设计并合成了一种两亲性聚合物mPEG-HA(SA)-DNs，用于制备一种多功能胶束系统，以增强紫杉醇（PTX）的治疗效果并降低其毒性。该聚合物是通过将mPEG、硬脂酸（SA）和2,4-二硝基苯磺酸（DNs）引入透明质酸（HA）骨架中制备的。通过上述修饰，制备的胶束可以高药物载荷地将PTX封装在其核心中。优化的PTX载药胶束的平均尺寸为158.3 nm。通过mPEG的作用，mPEG-HA(SA)-DNs胶束减少了非特异性蛋白质吸附。体外药物释放研究表明，胶束具有优异的谷胱甘肽（GSH）触发的PTX释放行为。此外，GSH可以触发DNs段从mPEG-HA(SA)-DNs中脱离，并释放SO2。体外和体内抗肿瘤疗效研究表明，PTX载药的mPEG-HA(SA)-DNs胶束显示出出色的抑制肿瘤效果。该胶束有潜力成为SO2和PTX联合癌症治疗的载体。版权所有 © 2023. 由Elsevier B.V.出版。

In this study, an amphiphilic polymer mPEG-HA(SA)-DNs was designed and synthesized to fabricate a multifunctional micellar system to enhance the therapeutic efficacy and reduce the toxic effect of paclitaxel (PTX). The polymer was prepared by introducing mPEG, stearic acid (SA) and 2,4-dinitrobenzenesulfonic acid (DNs) to the backbone of hyaluronic acid (HA). With above modifications, the fabricated micelles could encapsulate PTX in the core with high drug loading. The optimized PTX-loaded micelles had a mean size of 158.3 nm. Upon the effect of mPEG, the mPEG-HA(SA)-DNs micelles reduced the non-specific protein adsorption. In vitro drug release study revealed the excellent glutathione (GSH)-triggered PTX release behavior of the micelles. Moreover, GSH could trigger the detachment of DNs segment from mPEG-HA(SA)-DNs, and result in the release of SO2. In vitro and in vivo antitumor efficacy studies demonstrated that the PTX-loaded mPEG-HA(SA)-DNs micelles exhibited outstanding tumor suppression effect. The micelles would be potential carriers for combination cancer therapy by SO2 and PTX.Copyright © 2023. Published by Elsevier B.V.