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首页> 外文期刊>ACS applied materials & interfaces >Redox-Sensitive and Intrinsically Fluorescent Photoclick Hyaluronic Acid Nanogels for Traceable and Targeted Delivery of Cytochrome c to Breast Tumor in Mice
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Redox-Sensitive and Intrinsically Fluorescent Photoclick Hyaluronic Acid Nanogels for Traceable and Targeted Delivery of Cytochrome c to Breast Tumor in Mice

机译：氧化还原敏感和固有荧光的photoclick透明质酸纳米凝胶，可用于细胞色素c的可追踪和靶向递送至小鼠乳腺肿瘤。

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In spite of their high specificity and potency, few protein therapeutics are applied in clinical cancer therapy owing to a lack of safe and efficacious delivery systems. Here, we report that redox-sensitive and intrinsically fluorescent photoclick hyaluronic acid nanogels (HA-NGs) show highly efficient loading and breast tumor-targeted delivery of cytochrome c (CC). HA-NGs were obtained from hyaluronic acid-graft-oligo(ethylene glycol)-tetrazole (HA-OEG-Tet) via inverse nanoprecipitation and catalyst-free photoclick cross linking with L-cystine dimethacrylamide (MA-Cys-MA). HA-NGs exhibited a superb CC loading content of up to 40.6 wt %, intrinsic fluorescence (lambda(em) = 510 nm), and a small size of ca. 170 nm. Notably, CC-loaded nanogels (CC-NGs) showed a fast glutathione-responsive protein release behavior. Importantly, released CC maintained its bioactivity. MTT assays revealed that CC-NGs were highly potent with a low IC50 of 3.07 mu M to CD44+ MCF-7 human breast tumor cells. Confocal microscopy observed efficient and selective internalization of fluorescent HA-NGs into MCF-7 cells. Interestingly, HA-NGs exhibited also effective breast tumor penetration. The therapeutic results demonstrated that CC-NGs effectively inhibited the growth of MCF-7 breast tumor xenografts at a particularly low dose of 80 or 160 nmol CC equiv./kg. Moreover, CC-NGs did not cause any change in mice body weight, corroborating their low systemic side effects. Redox-sensitive and intrinsically fluorescent photoclick hyaluronic acid nanogels have appeared as a "smart" protein delivery nanoplatform enabling safe, efficacious, traceable, and targeted cancer protein therapy in vivo.
机译：尽管它们具有高特异性和效力，但由于缺乏安全有效的递送系统，因此很少将蛋白质治疗剂用于临床癌症治疗。在这里，我们报告氧化还原敏感和本质上是荧光的光点击透明质酸纳米凝胶（HA-NGs）显示出高效的负载和乳腺癌靶向细胞色素c（CC）的交付。 HA-NGs是由透明质酸接枝的寡聚（乙二醇）-四唑（HA-OEG-Tet）通过逆纳米沉淀法和与L-胱氨酸二甲基丙烯酰胺（MA-Cys-MA）进行的无催化剂光点击交联而获得的。 HA-NGs的CC负载量高达40.6 wt％，固有荧光（λ（em）= 510 nm），并且尺寸很小。 170 nm。值得注意的是，载有CC的纳米凝胶（CC-NGs）显示出快速的谷胱甘肽反应性蛋白释放行为。重要的是，释放的CC保持了其生物活性。 MTT分析显示，CC-NGs对CD44 + MCF-7人乳腺肿瘤细胞的IC50为3.07μM，效率很高。共聚焦显微镜观察到荧光HA-NGs有效且选择性地内在化进入MCF-7细胞。有趣的是，HA-NGs还表现出有效的乳腺肿瘤渗透性。治疗结果表明，CC-NGs以80或160 nmol CC当量/ kg的低剂量有效抑制MCF-7乳腺癌异种移植物的生长。而且，CC-NGs不会引起小鼠体重的任何变化，从而证实了它们的低全身性副作用。氧化还原敏感和本质上具有荧光作用的photoclick透明质酸纳米凝胶已经出现为“智能”蛋白质递送纳米平台，可在体内进行安全，有效，可追溯和靶向的癌症蛋白质治疗。

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