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Synthesis and Characterization of Fatty Acid Grafted Chitosan Polymer and Their Nanomicelles for Nonviral Gene Delivery Applications
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2017-10-23 00:00:00 , DOI: 10.1021/acs.bioconjchem.7b00505 Divya Sharma 1 , Jagdish Singh 1
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2017-10-23 00:00:00 , DOI: 10.1021/acs.bioconjchem.7b00505 Divya Sharma 1 , Jagdish Singh 1
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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.
中文翻译：
脂肪酸接枝的壳聚糖聚合物及其分子筛的合成，表征及其在非病毒基因传递中的应用
这项研究的目的是合成和表征脂肪酸接枝的壳聚糖（脂肪酸-g -CS）聚合物及其纳米胶束，以用作基因传递的载体。CS使用增加的脂肪酰基链长度的饱和脂肪酸进行疏水改性。碳二亚胺和N-羟基琥珀酰亚胺用于将脂肪酸的羧基与CS的胺基偶联。质子核磁共振和傅立叶变换红外光谱用于量化脂肪酰基取代到CS骨架上。使用尺寸排阻高效液相色谱法测定了合成聚合物的分子量分布，发现该分子量在母体CS聚合物的范围内（〜50 kDa）。使用pyr作为荧光探针确定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。两亲脂肪酸-克-CS聚合物在水性环境中自组装，形成〜200 nm粒径的纳米胶束，由于CS分子上游离伯氨基的阳离子性质，其净电荷略带正电荷。这些高分子纳米胶束分别通过体外溶血和MTT细胞活力测定法表现出优异的血液和细胞相容性，与未修饰的脱乙酰壳多糖和裸露的DNA相比，转染效率更高。这些纳米胶束的表面可以用配体进行进一步修饰，从而实现选择性靶向，增强的细胞结合和内在化。因此，可以将这些纳米胶束用作潜在的非病毒基因递送载体，以进行安全有效的基因治疗。
更新日期：2017-10-23
中文翻译：
脂肪酸接枝的壳聚糖聚合物及其分子筛的合成，表征及其在非病毒基因传递中的应用
这项研究的目的是合成和表征脂肪酸接枝的壳聚糖（脂肪酸-g -CS）聚合物及其纳米胶束，以用作基因传递的载体。CS使用增加的脂肪酰基链长度的饱和脂肪酸进行疏水改性。碳二亚胺和N-羟基琥珀酰亚胺用于将脂肪酸的羧基与CS的胺基偶联。质子核磁共振和傅立叶变换红外光谱用于量化脂肪酰基取代到CS骨架上。使用尺寸排阻高效液相色谱法测定了合成聚合物的分子量分布，发现该分子量在母体CS聚合物的范围内（〜50 kDa）。使用pyr作为荧光探针确定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。两亲脂肪酸-克-CS聚合物在水性环境中自组装，形成〜200 nm粒径的纳米胶束，由于CS分子上游离伯氨基的阳离子性质，其净电荷略带正电荷。这些高分子纳米胶束分别通过体外溶血和MTT细胞活力测定法表现出优异的血液和细胞相容性，与未修饰的脱乙酰壳多糖和裸露的DNA相比，转染效率更高。这些纳米胶束的表面可以用配体进行进一步修饰，从而实现选择性靶向，增强的细胞结合和内在化。因此，可以将这些纳米胶束用作潜在的非病毒基因递送载体，以进行安全有效的基因治疗。
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