Key Laboratory of Functional Inorganic Materials Chemistry, Ministry of Education, School of Chemistry and Material Science, Heilongjiang University, Harbin 150080, China.
College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin 150025, China.
Int J Biol Macromol. 2023 Dec 31;253(Pt 1):126624. doi: 10.1016/j.ijbiomac.2023.126624. Epub 2023 Aug 30.
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 SO. 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 SO and PTX.
在这项研究中，设计并合成了一种两亲性聚合物 mPEG-HA(SA)-DNs，以构建一种多功能胶束系统，以提高紫杉醇（PTX）的治疗效果并降低其毒性作用。该聚合物通过将 mPEG、硬脂酸（SA）和 2,4-二硝基苯磺酸（DNs）引入透明质酸（HA）的主链来制备。通过以上修饰，所制备的胶束可以将 PTX 包封在核心中，具有较高的载药量。优化后的载 PTX 胶束的平均粒径为 158.3nm。在 mPEG 的作用下，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 片段从 mPEG-HA(SA)-DNs 上的分离，并导致 SO 的释放。体外和体内抗肿瘤功效研究表明，载 PTX 的 mPEG-HA(SA)-DNs 胶束表现出出色的肿瘤抑制效果。该胶束将是通过 SO 和 PTX 联合癌症治疗的潜在载体。
