We propose hyaluronic acid (HA)-based nanoparticles for cancer-specific combination therapy, delivering ursolic acid (UA) and the anticancer drug doxorubicin (DOX). HA was conjugated with UA via disulfide bonds (i.e., HA-ss-UA), enabling self-assembly into nanoparticles with a hydrophobic UA core and thereby, effective encapsulation of hydrophobic DOX. The nanoparticles facilitated internalization into cancer cells due to interactions between HA and CD44 receptors. In a cancer-specific, glutathione-rich environment, the disulfide bonds in the nanoparticles were cleaved effectively, releasing more than 90% of the conjugated UA and DOX sustainably for 2 days. In vitro testing with A549 cancer cells showed enhanced endocytosis and anticancer efficacy of the nanoparticles. Intratumoral delivery of the nanoparticles to A549-bearing mice demonstrated the most potent anticancer effect compared to other delivery formulations. Therefore, the anticancer drug-loaded nanoparticles, composed of HA conjugated with UA via disulfide bonds, represent a promising formulation for cancer-specific combination therapy.

中文翻译：

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自组装的抗癌药物负载透明质酸纳米颗粒与熊果酸偶联用于增强联合化疗


我们提议将基于透明质酸 （HA） 的纳米颗粒用于癌症特异性联合治疗，提供熊果酸 （UA） 和抗癌药物阿霉素 （DOX）。HA 通过二硫键（即 HA-ss-UA）与 UA 偶联，能够自组装成具有疏水性 UA 核心的纳米颗粒，从而有效封装疏水性 DOX。由于 HA 和 CD44 受体之间的相互作用，纳米颗粒促进了癌细胞的内化。在癌症特异性、富含谷胱甘肽的环境中，纳米颗粒中的二硫键被有效裂解，可持续释放超过 90% 的偶联 UA 和 DOX，持续 2 天。对 A549 癌细胞的体外测试显示纳米颗粒的内吞作用和抗癌功效增强。与其他递送制剂相比，将纳米颗粒瘤内递送给携带 A549 的小鼠显示出最有效的抗癌作用。因此，由通过二硫键与 UA 偶联的 HA 组成的载药纳米颗粒代表了癌症特异性联合治疗的有前途的配方。