Engelberth Sarah A, Hempel Nadine, Bergkvist Magnus
†Nanobioscience Constellation, College of Nanoscale Science and Engineering, SUNY Polytechnic Institute, Albany, New York 12203, United States.
‡Department of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania 17033, United States.
Bioconjug Chem. 2015 Aug 19;26(8):1766-74. doi: 10.1021/acs.bioconjchem.5b00313. Epub 2015 Aug 11.
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 6 days while exhibiting less toxicity than a common liposome-based siRNA delivery reagent, Lipofectamine RNAiMAX. These promising results set the stage for the 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.
纳米结构淀粉是天然衍生的纳米材料,可通过化学修饰引入官能团,增强其在药物递送和其他生物技术应用方面的潜力。在这项概念验证研究中,我们研究了经化学修饰的酶促合成糖原(ESG)纳米树枝状分子作为一种可生物降解、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进行修饰,通过环氧开环反应引入季铵基团。这种阳离子ESG(cESG)通过静电作用结合siRNA,并在体外卵巢透明细胞癌模型中成功下调了蛋白表达。该构建体可实现长达6天的持续siRNA递送,同时与常用的基于脂质体的siRNA递送试剂Lipofectamine RNAiMAX相比,毒性更小。这些令人鼓舞的结果为将树枝状淀粉用作一种经济高效、易于修饰的纳米级递送系统奠定了基础,该系统可用于递送包括核酸和治疗性化合物在内的多种货物。