Synthesis and Characterization of Fatty Acid Grafted Chitosan Polymer and Their Nanomicelles for Nonviral Gene Delivery Applications.
Synthesis and Characterization of Fatty Acid Grafted Chitosan Polymer and Their Nanomicelles for Nonviral Gene Delivery Applications.
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DOI：
10.1021/acs.bioconjchem.7b00505
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发表时间：
2017-11-15
影响因子：
4.7
通讯作者：
Singh J
中科院分区：
文献类型：
--
作者：
Sharma D;Singh J
本研究的目的是合成和表征脂肪酸接枝壳聚糖（fatty acid-g-CS）聚合物及其纳米胶束作为基因传递载体。使用增加脂肪酰基链长度的饱和脂肪酸对CS进行疏水改性。碳二亚胺沿着N-羟基丁二酰亚胺用于将脂肪酸的羧基与CS的胺基偶联。质子核磁共振和傅里叶变换红外光谱被用来量化CS骨架上的脂肪酰基取代。使用尺寸排阻高效液相色谱法测定合成的聚合物的分子量分布，发现其在母体CS聚合物的范围内（~50 kDa）。以芘为荧光探针测定了聚合物的临界胶束浓度（cmc）。发现cmc随着脂肪酰基链长度的增加而降低。两亲性脂肪酸-g-CS聚合物在水溶液中自组装形成粒径约为200 nm的纳米胶束，由于CS分子上游离伯氨基的阳离子性质，其净电荷略带正电。这些聚合物纳米胶束表现出优异的血液和细胞相容性，分别通过体外溶血和MTT细胞活力测定，并显示出上级的转染效率相比，未修饰的壳聚糖和裸DNA。这些纳米胶束的表面可以进一步用配体修饰，从而允许选择性靶向、增强的细胞结合和内化。因此，这些纳米胶束可以被利用作为潜在的非病毒基因递送载体，用于安全和有效的基因治疗。
The aim of this study was to synthesize and characterize fatty acid-grafted-chitosan (fatty acid-g-CS) polymer and their nanomicelles for use as carriers for gene delivery. CS was hydrophobically modified using saturated fatty acids of increasing fatty acyl chain length. Carbodiimide along with N-hydroxysuccinimide was used for coupling carboxyl group of fatty acids with amine groups of CS. Proton nuclear magnetic resonance and Fourier transform infrared spectroscopy were used to quantify fatty acyl substitution onto CS backbone. The molecular weight distribution of the synthesized polymers was determined using size exclusion high performance liquid chromatography and was found to be in range of the parent CS polymer (~50 kDa). The critical micelle concentration (cmc) of the polymers was determined using pyrene as a fluorescent probe. The cmc was found to decrease with an increase in fatty acyl chain length. The amphiphilic fatty acid-g-CS polymers self-assembled in an aqueous environment to form nanomicelles of ~200 nm particle size and slightly positive net charge due to the cationic nature of free primary amino groups on CS molecule. These polymeric nanomicelles exhibited excellent hemo- and cytocompatibility, as evaluated by in vitro hemolysis and MTT cell viability assay, respectively, and showed superior transfection efficiency compared to unmodified chitosan and naked DNA. The surface of these nanomicelles can be further modified with ligands allowing for selective targeting, enhanced cell binding, and internalization. These nanomicelles can thus be exploited as potential nonviral gene delivery vectors for safe and efficient gene therapy.
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影响因子：
15
作者：
KALYANASUNDARAM, K;THOMAS, JK
通讯作者：
THOMAS, JK
影响因子：
8
作者：
Fröhlich E
通讯作者：
Fröhlich E
影响因子：
5.8
作者：
Hu, Fu-Qiang;Zhao, Meng-Dan;Zeng, Su
通讯作者：
Zeng, Su
DOI：
10.1016/s0731-7085(03)00155-9
发表时间：
2003-08-21
影响因子：
3.4
作者：
Lavertu, M;Xia, Z;Gupta, A
通讯作者：
Gupta, A
影响因子：
14
作者：
Andersen, Morten O.;Lichawska, Agata;Howard, Kenneth A.
通讯作者：
Howard, Kenneth A.