Dual-Cross-Linked Methacrylated Alginate Sub-Microspheres for Intracellular Chemotherapeutic Delivery.
Dual-Cross-Linked Methacrylated Alginate Sub-Microspheres for Intracellular Chemotherapeutic Delivery.
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DOI：
10.1021/acsami.6b03245
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发表时间：
2016-07-20
影响因子：
9.5
通讯作者：
Floreani RA
中科院分区：
文献类型：
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作者：
Fenn SL;Miao T;Scherrer RM;Floreani RA
开发了由甲基丙烯酸化藻酸盐（Alg-MA）组成的细胞内递送载体，用于盐酸阿霉素（DOX）的内化和释放。通过无水反应合成Alg-MA，并使用水/油乳液将Alg-MA和DOX的混合物形成为亚微球。通过暴露于绿色光形成交联的亚微球，以研究与传统技术如紫外（UV）光相比交联对药物释放和细胞内化的影响。单独使用光暴露或与使用氯化钙（CaCl 2）的离子交联组合进行交联。Alg-MA亚微球的直径在88 - 617 nm之间，zeta电位在-20和-37 mV之间。使用人肺上皮癌细胞（A549）作为模型，使用流式细胞术确认细胞内化;不同的亚微球制剂改变内化效率，其中UV交联的亚微球实现最高内化百分比。虽然空白（未加载的）Alg-MA亚微球对A549无细胞毒性，但加载DOX的亚微球在培养5天后显著降低线粒体活性。光交联Alg-MA亚微球可能是一种潜在的肿瘤化疗药物递送系统。
Intracellular delivery vehicles comprised of methacrylated alginate (Alg-MA) were developed for the internalization and release of doxorubicin hydrochloride (DOX). Alg-MA was synthesized via an anhydrous reaction, and a mixture of Alg-MA and DOX was formed into sub-microspheres using a water/oil emulsion. Covalently crosslinked sub-microspheres were formed via exposure to green light, in order to investigate effects of crosslinking on drug release and cell internalization, compared to traditional techniques such as ultra violet (UV) light. Crosslinking was performed using light exposure alone, or in combination with ionic crosslinking using calcium chloride (CaCl2). Alg-MA sub-microsphere diameters were between 88 – 617 nm, and zeta-potentials were between −20 and −37 mV. Using human lung epithelial carcinoma cells (A549s) as a model, cellular internalization was confirmed using flow cytometry; different sub-microsphere formulations varied the efficiency of internalization, with UV-crosslinked sub-microspheres achieving the highest internalization percentages. While blank (non-loaded) Alg-MA sub-microspheres were non-cytotoxic to A549s, DOX-loaded sub-microspheres significantly reduced mitochondrial activity after five days of culture. Photo-crosslinked Alg-MA sub-microspheres may be a potential chemotherapeutic delivery system for cancer treatment.