Chitosan hydrogel for localized gene silencing
Chitosan hydrogel for localized gene silencing
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DOI：
10.4161/cbt.11.9.15185
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发表时间：
2011-05-01
影响因子：
3.6
通讯作者：
Sood, Anil K.
中科院分区：
文献类型：
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作者：
Han, Hee Dong;Mora, Edna M.;Sood, Anil K.
目的：结果：壳聚糖水凝胶（CH-HG）具有温度依赖性的液-固相转变，注射后在肿瘤组织中形成吸热型水凝胶，并在肿瘤组织中形成了一种新的靶细胞靶向siRNA的局部给药系统。此外，我们测试了将Alexa 555 siRNA/CH-HG单次肿瘤内注射到携带A375 SM的小鼠中后的体内递送程度。与对照相比，Alexa 555 siRNA表现出更高的肿瘤细胞定位。Alexa 555 siRNA递送延伸到CH-HG外部的肿瘤细胞，并且一些肿瘤细胞也浸润到CH-HG中。对于治疗性概念验证研究，包括TG 2靶向siRNA的CH-HG显著抑制黑色素瘤（A375 SM）和乳腺癌中的肿瘤生长。（MDA-MB 231）肿瘤模型与对照相比（A375 SM：72%减少和MDA-MB 231：92%减少，p < 0.001）。我们制备了一种装载有siRNA的CH-HG系统，以增强局部治疗效果，而没有全身副作用的风险。通过荧光显微镜证实siRNA递送到CH-HG中。在小鼠黑色素瘤（A375 SM）和乳腺癌（MDA-MD 231）cancer.Conclusions模型中检查抗肿瘤功效：本研究开发了一种新的局部递送方法，使用CH-HG系统进行siRNA治疗。这种方法可以广泛应用于多种局部疾病。
Objective: To achieve effective delivery of siRNA into target cells in vivo, we have developed a novel approach of siRNA delivery by using local drug delivery systems.Results: The chitosan hydrogel (CH-HG) displayed a liquid-solid phase transition in a temperature-dependent manner and formed an endothermic hydrogel in tumor tissue after intra-tumoral injection. Additionally, we tested the extent of in vivo delivery following a single intra-tumoral injection of Alexa555 siRNA/CH-HG into A375SM-bearing mice. The Alexa555 siRNA demonstrated higher localization into tumor cells compared to control. The Alexa555 siRNA delivery extends to tumor cells outside of CH-HG and some tumor cells also infiltrated into CH-HG. For therapeutic proof-of-concept studies, CH-HG including TG2-targeted siRNA significantly inhibited tumor growth in melanoma (A375SM) and breast (MDA-MB231) tumor models compared to control (A375SM: 72% reduction and MDA-MB231: 92% reduction, p < 0.001).Experimental Design: We prepared a CH-HG system loaded with siRNA to enhance localized therapeutic efficacy without risk for systemic side effects. Delivery of siRNA into CH-HG was confirmed by fluorescence microscopy. Antitumor efficacy was examined in mouse models of melanoma (A375SM) and breast (MDA-MD231) cancer.Conclusions: This study developed a novel local delivery method for siRNA therapy using the CH-HG system. This approach could have broad applications for multiple localized diseases.