Abstract The present research aims at controlled delivery of anticancer drugs camptothecin and doxorubicin through encapsulation in self-assembled hyaluronic acid (HA)-testosterone conjugates. The conjugates were obtained by functionalization of either natural sodium hyaluronate or hydrazide-modified HA derivatives with testosterone hemisuccinate. From 2.0 to 7.7% of HA disaccharide units were linked to testosterone via two types of linkers of different length. Fourier transform infrared and proton nuclear magnetic resonance spectroscopies confirmed modification of HA. Conjugation of hydrophobic testosterone to hydrophilic backbone of HA resulted in the self-assembly of amphiphilic HA-testosterone conjugates in aqueous medium and the formation of stable and negatively charged nanoparticles with hydrodynamic diameter ranging from 172 to 380 nm and ζ-potential ranging from −37 to −26 mV, as evidenced from dynamic light scattering measurements. Examination of the dried conjugates by transmission electron microscopy revealed almost spherical particles of 50–100 nm size. Entrapment of camptothecin and doxorubicin in the hydrophobic core of HA-testosterone nanoparticles was performed with the drugs content of ca. 2.8 wt% and 3.5 wt% respectively. The sustained release of the anticancer drugs over 96 h was observed in phosphate buffered saline at pH 7.4. Cytotoxicity of camptothecin- and doxorubicin-loaded HA-testosterone nanoparticles against MCF-7 cancer cell line was found to be similar to the cytotoxicity of the free anticancer drugs. Based on the results of the in vitro studies, we can conclude that the developed HA-testosterone nanoparticles are promising candidates in chemotherapy treatments of cancers.

中文翻译：

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自组装透明质酸-睾酮纳米载体用于递送抗癌药物

摘要 本研究旨在通过封装在自组装透明质酸 (HA)-睾酮缀合物中来控制递送抗癌药物喜树碱和阿霉素。通过用睾酮半琥珀酸酯官能化天然透明质酸钠或酰肼修饰的HA衍生物获得缀合物。2.0% 到 7.7% 的 HA 双糖单位通过两种不同长度的接头与睾酮连接。傅里叶变换红外和质子核磁共振光谱证实了 HA 的修饰。疏水性睾酮与 HA 的亲水主链的结合导致两亲性 HA-睾酮结合物在水性介质中自组装，并形成稳定且带负电荷的纳米粒子，其流体动力学直径范围为 172 至 380 nm，ζ 电位范围为 -37至−26 mV，如动态光散射测量所示。通过透射电子显微镜检查干燥的缀合物显示几乎为 50-100 nm 大小的球形颗粒。喜树碱和多柔比星在 HA-睾酮纳米颗粒的疏水核心中的包埋是在药物含量约为 分别为 2.8 重量％和 3.5 重量％。在 pH 7.4 的磷酸盐缓冲盐水中观察到抗癌药物的持续释放超过 96 小时。发现喜树碱和阿霉素负载的 HA-睾酮纳米颗粒对 MCF-7 癌细胞系的细胞毒性与游离抗癌药物的细胞毒性相似。根据体外研究的结果，我们可以得出结论，开发的 HA-睾酮纳米颗粒是癌症化疗治疗的有希望的候选者。