A natural polysaccharide-based nanogel has been synthesized and characterized as pH-sensitive drug delivery system for poorly water-soluble anticancer drugs. In this work, methacrylated hyaluronic acid (MAHA) was used to prepared acid degradable nanogels by a surfactant-free polymerization method in water, where 2,2-dimethacroyloxy-1-ethoxypropane (DMAEP) served as a pH labile cross-linker. Nanogels of different cross-linking density were prepared and doxorubicin (DOX) was successfully encapsulated into the nanogels with drug-loading contents (DLC) ranging from 7.67 to 12.15%. An accelerated DOX release was found in acidic conditions. Cytotoxicity study showed that the DOX loaded nanogels have significantly enhanced cytotoxicity in vitro compared with the nonsensitive ones. Confocal microscopy revealed that there was more DOX in the nuclei of tumor cells when incubated with DOX-loaded pH sensitive nanogels for 3 to 12 h. The enhanced anticancer activity of DOX-loaded pH-sensitive nanogels was also verified by in vivo therapeutic study on mice, in which tumor volume evolution was measured and tumor tissues cell apoptosis and proliferation was examined.

中文翻译：

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基于透明质酸的pH敏感纳米凝胶，用于靶向肿瘤的药物递送

已经合成了天然的基于多糖的纳米凝胶，并将其表征为水溶性差的抗癌药物的pH敏感药物递送系统。在这项工作中，使用甲基丙烯酸化的透明质酸（MAHA）通过无表面活性剂在水中的聚合方法制备酸可降解的纳米凝胶，其中2,2-二甲基丙烯酰氧基-1-乙氧基丙烷（DMAEP）作为pH不稳定的交联剂。制备了具有不同交联密度的纳米凝胶，并将阿霉素（DOX）成功地囊封在纳米凝胶中，其载药量（DLC）为7.67％至12.15％。在酸性条件下发现DOX释放加快。细胞毒性研究表明，与非敏感性纳米凝胶相比，载有DOX的纳米凝胶在体外具有显着增强的细胞毒性。共聚焦显微镜显示，当与载有DOX的pH敏感纳米凝胶孵育3至12 h时，肿瘤细胞的核中有更多的DOX。通过对小鼠的体内治疗研究，还证实了装载DOX的pH敏感纳米凝胶的增强的抗癌活性，其中测量了肿瘤的体积演变并检查了肿瘤组织细胞的凋亡和增殖。