Redox-Sensitive Hyaluronic Acid Polymer Prodrug Nanoparticles for Enhancing Intracellular Drug Self-Delivery and Targeted Cancer Therapy,ACS Biomaterials Science & Engineering

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Redox-Sensitive Hyaluronic Acid Polymer Prodrug Nanoparticles for Enhancing Intracellular Drug Self-Delivery and Targeted Cancer Therapy
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2020-06-08 , DOI: 10.1021/acsbiomaterials.0c00762
Beibei Lu _{1,

2} , Fan Xiao ₃ , Zhenyuan Wang _{1,

2} , Binshen Wang _{1,

2} , Zuchen Pan _{1,

2} , Weiwei Zhao _{1,

2} , Zhenye Zhu _{1,

2} , Jiaheng Zhang _{1,

2}

Affiliation

Currently, available nanoscale anticancer drug delivery systems have low targeting and release efficiency, limiting their therapeutic effects. Thus, tumor-targeting nanocarriers for self-assembly of amphiphilic polymer–drug conjugates are urgently needed to improve drug targeting and treatment efficacy. Here, we report the construction of a stable, reduction-sensitive prodrug conjugate based on hyaluronic acid-grafted pH-sensitive doxorubicin (DOX). The amphiphilic prodrug copolymer self-assembled into spherical nanoparticles in aqueous solution and exhibited an average diameter of 150 nm. Prodrug micelles were stable in a normal physiological environment and achieve selective and rapid release under acidic pH and/or high reduction conditions. Cell Counting Kit-8, flow cytometry, and live cell imaging assays showed that the prodrug had high targeting and antitumor activity against CD44 receptors. Moreover, in vivo pharmacokinetics and biodistribution studies showed that the prodrug had a longer circulation time in BALB/c mice and higher accumulation in 4T1 tumors. Interestingly, the prodrug could effectively treat tumors with few side effects. These results showed that the DOX prodrug micelles developed in this study may have great potential in targeted therapy.

中文翻译：

氧化还原敏感的透明质酸聚合物前药纳米颗粒，用于增强细胞内药物的自我传递和靶向癌症治疗。

当前，可用的纳米级抗癌药物递送系统具有低靶向和释放效率，限制了它们的治疗效果。因此，迫切需要用于两亲性聚合物-药物结合物自组装的靶向肿瘤的纳米载体，以改善靶向药物和治疗效果。在这里，我们报告基于透明质酸接枝的pH敏感阿霉素（DOX）的稳定，还原敏感的前药缀合物的建设。两亲性前药共聚物在水溶液中自组装成球形纳米颗粒，并且表现出150nm的平均直径。前药胶束在正常的生理环境中是稳定的，并且在酸性pH和/或高还原条件下实现选择性和快速释放。Cell Counting Kit-8，流式细胞仪，活细胞成像分析表明，前药对CD44受体具有高靶向性和抗肿瘤活性。此外，体内药代动力学和生物分布研究表明，前药在BALB / c小鼠中具有更长的循环时间，在4T1肿瘤中具有更高的积累。有趣的是，前药可以有效地治疗肿瘤而几乎没有副作用。这些结果表明，在这项研究中开发的DOX前药胶束在靶向治疗中可能具有巨大潜力。

更新日期：2020-07-13

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