Although various nanocarriers have been developed to deliver anticancer drugs to the target tumors, it is still remaining great challenges, including burst release, non-specific targetability and insufficient therapeutic efficacy. Herein, we prepared a multifunctional nanoparticle composed of Ag core and hyaluronic acid shell (Ag NPs@HA) for stimultaneously intracellular delivery of Doxorubicin (DOX) and Ag NPs to improve the anticancer therapeutic efficacy. For our approach, Ag NPs was simply synthesized via the redox reaction between Ag ions and catechol group of functional HA, and DOX was subsequently loaded into the HA-coated Ag NPs through the interaction between the remaining catechol groups and DOX (Ag NPs@HA/DOX). The particles exhibited uniform morphology, good biocompatibility to normal cells, and pH-sensitive drug release. Notably, thanks to the specific interaction of HA and CD44 receptor-overexpressing cancer cells, Ag NPs@HA/DOX could dramatically improve the anti-tumor efficacy as well as mimicking 3D spheroid model, compared to the free DOX. Moreover, Ag NPs@HA/DOX exhibited superior tumor supression on a HELA-xenografted mouse model, while minimizing the systemic toxicity of free DOX. From the obtained results, we suggest Ag NPs@HA as potential nanocarrier for targeting delivery of various therapeutic drugs in anticancer therapy.

中文翻译：

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透明质酸包被的银纳米粒子释放阿霉素用于组合抗肿瘤治疗


尽管已经开发出多种纳米载体来将抗癌药物递送至靶肿瘤，但仍面临巨大的挑战，包括爆发释放、非特异性靶向性和治疗效果不足。在此，我们制备了一种由银核和透明质酸壳组成的多功能纳米颗粒（Ag NPs@HA），用于在细胞内同时递送阿霉素（DOX）和Ag NPs，以提高抗癌治疗效果。在我们的方法中，Ag NPs是通过Ag离子和功能性HA的儿茶酚基团之间的氧化还原反应简单合成的，随后通过剩余的儿茶酚基团和DOX之间的相互作用将DOX加载到HA包被的Ag NPs中（Ag NPs@HA） /阿霉素）。该颗粒表现出均匀的形态、与正常细胞良好的生物相容性以及pH敏感的药物释放。值得注意的是，由于HA和CD44受体过表达癌细胞的特异性相互作用，与游离DOX相比，Ag NPs@HA/DOX可以显着提高抗肿瘤功效并模仿3D球体模型。此外，Ag NPs@HA/DOX 在 HELA 异种移植小鼠模型上表现出优异的肿瘤抑制作用，同时最大限度地减少游离 DOX 的全身毒性。根据所获得的结果，我们建议 Ag NPs@HA 作为潜在的纳米载体，用于抗癌治疗中靶向递送各种治疗药物。