Chemically Modified Dendritic Starch: A Novel Nanomaterial for siRNA Delivery.
Chemically Modified Dendritic Starch: A Novel Nanomaterial for siRNA Delivery.
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DOI：
10.1021/acs.bioconjchem.5b00313
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发表时间：
2015-08-19
影响因子：
4.7
通讯作者：
Bergkvist M
中科院分区：
文献类型：
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作者：
Engelberth SA;Hempel N;Bergkvist M
纳米结构淀粉是天然衍生的纳米材料，可以进行化学改性以允许引入官能团，从而增强其用于药物递送和其他生物技术应用的潜力。在这个概念研究的证明中，我们研究了化学修饰的酶促合成的糖原（ESG）纳米树突作为一种可生物降解的，生物相容的siRNA递送系统。使用缩水甘油基三甲基氯化铵（GTMA）对市售ESG进行改性，通过环氧化物开环反应引入季铵基团。这种阳离子ESG（cESG）静电结合siRNA并在体外卵巢透明细胞癌模型中成功敲低蛋白表达。该构建体表现出持续的siRNA递送长达六天，同时表现出比常见的基于脂质体的siRNA递送试剂Lipofectamine RNAiMAX更低的毒性。这些有希望的结果为使用树枝状淀粉作为一种具有成本效益的，易于修改的纳米级递送系统，用于包括核酸和治疗化合物在内的各种货物奠定了基础。
Nanostructured starches are naturally derived nanomaterials that can be chemically modified to allow for the introduction of functional groups, enhancing their potential for drug delivery and other biotechnology applications. In this proof of concept study, we investigate chemically modified, enzymatically synthesized glycogen (ESG) nanodendrites as a biodegradable, biocompatible, siRNA delivery system. Commercially available ESG was modified using glycidyltrimethylammonium chloride (GTMA), introducing quaternary ammonium groups via an epoxide ring opening reaction. This cationic ESG (cESG) electrostatically bound siRNA and successfully knocked-down protein expression in an in vitro ovarian clear cell carcinoma model. The construct exhibited sustained siRNA delivery for up to six days while exhibiting less toxicity than a common liposome-based siRNA delivery reagent, Lipofectamine RNAiMAX. These promising results set the stage for use of dendritic starch as a cost-effective, easily modifiable nanoscale delivery system for a diverse range of cargo including nucleic acids and therapeutic compounds.