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首页> 外文期刊>RSC Advances >Redox-responsive cystamine conjugated chitin-hyaluronic acid composite nanogels
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Redox-responsive cystamine conjugated chitin-hyaluronic acid composite nanogels

机译：氧化还原反应性胱胺共轭几丁质-透明质酸复合纳米凝胶

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摘要

Nanoscale carriers were developed to overcome the challenging barriers for the targeted intracellular delivery of chemotherapeutic agents, in particular within tumors. We demonstrate redox responsive cystamine (Cys) conjugated hyaluronic acid (HA)-chitin (CNG) nanogels for the intracellular delivery of doxorubicin (DOX) within colon cancer cells. Chitin, having a slow degrading property, could make HA to slowly degrade, thus protecting the DOX from a sudden burst release, and HA, being a ligand for the CD44 receptor, are over expressed in colon cancer cells (HT-29). 150-200 nm sized DOX-HA-CNGs and DOX-HA-Cys-CNGs were developed and characterized by DLS, Zeta, TG/DTA, FT-IR, EDAX and rheological techniques. The composite nanogel preparations proved to be safe for intravenous administration because they were non-hemolytic and did not interfere with the coagulation cascade. Flow cytometric and fluorescent microscopic analysis proved the specific internalization of DOX-HA-CNGs within HT-29 cells (CD-44 +ve). MTT assay revealed the superior anti-proliferative activity of DOX-HA-Cys-CNGs in CD-44 +ve HT-29 cells compared to that in CD-44 -ve IEC-6 cells. Thus, HA-Cys-CNGs are proven to be a better carrier for the selective, redox responsive and intracellular delivery of DOX.
机译：开发了纳米级载体以克服针对化学治疗剂的细胞内递送的挑战性障碍，特别是在肿瘤内。我们展示了氧化还原反应性胱胺（Cys）缀合的透明质酸（HA）-几丁质（CNG）纳米凝胶用于结肠癌细胞内阿霉素（DOX）的细胞内递送。几丁质具有缓慢的降解性能，可以使HA缓慢降解，从而保护DOX免受突然的突释，并且作为CD44受体的配体的HA在结肠癌细胞（HT-29）中过度表达。通过DLS，Zeta，TG / DTA，FT-IR，EDAX和流变学技术开发并表征了150-200 nm尺寸的DOX-HA-CNG和DOX-HA-Cys-CNG。复合纳米凝胶制剂经证明是安全的，因为它们是非溶血性的，并且不会干扰凝血级联反应，因此对静脉内给药是安全的。流式细胞仪和荧光显微镜分析证明了DOX-HA-CNGs在HT-29细胞（CD-44 + ve）中的特异性内在化。 MTT分析显示，与CD-44-ve IEC-6细胞相比，DOX-HA-Cys-CNGs在CD-44 + ve HT-29细胞中具有优异的抗增殖活性。因此，HA-Cys-CNGs被证明是选择性，氧化还原响应和细胞内传递DOX的更好载体。

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