Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Pharmacol Rep. 2018 Jun;70(3):418-425. doi: 10.1016/j.pharep.2017.11.005. Epub 2017 Nov 20.
Prostate cancer is known as the most common malignancy in men. Chitosan has generated great interest as a useful biopolymer for the encapsulation of small interfering RNA (siRNA). Due to cationic nature, chitosan is able to efficiently encapsulate siRNA molecules and form nanoparticles. Furthermore, the biocompatible and biodegradable attributes of chitosan have paved the way for its potential application in the in vivo delivery of therapeutic siRNAs. In this study, we aimed to design chitosan/CMD nanoparticles for the efficient encapsulation of the anti-cancer drugs SN38 and Snail-specific siRNA.
Physicochemical characteristics, growth inhibitory properties, and anti-migratory capacities of the dual delivery of SN38-Snail siRNA CMD-chitosan nanoparticles were investigated in prostate cancer cells.
Our findings provided evidence for the suggestion that, ChNP-CMD-SN38-siRNA treated cells, the mRNA level of snail decreased from 1.00 to 0.30 (±0.14) and 0.09 (±0.04) after 24h and 48h, respectively. Additionally, the fold induction of E-cadherin and Claudin-1 increased from 1.00 to now 3.12 (±0.62), 3.02 (±0.28) after 24h and 5.6 (±0.91), 4.42 (±0.51) after 48h, respectively. Also, co-delivery of SN38 and Snail-specific siRNA by an appropriate nanocerrier (chitosan nanoparticles) could reduce the viability, proliferation, and migration of PC-3 cells.
In conclusion, ChNPs encapsulating SN38 and Snail-specific siRNA may represent huge potential as an effective anti-cancer drug delivery system for the treatment of prostate cancer.
前列腺癌是男性最常见的恶性肿瘤。壳聚糖作为一种有用的生物聚合物,已引起人们极大的兴趣,可用于包裹小干扰 RNA(siRNA)。由于壳聚糖带正电荷,因此能够有效地包裹 siRNA 分子并形成纳米颗粒。此外,壳聚糖的生物相容性和可生物降解特性为其在体内递送治疗性 siRNA 的潜在应用铺平了道路。在这项研究中,我们旨在设计壳聚糖/CMD 纳米颗粒,以有效封装抗癌药物 SN38 和 Snail 特异性 siRNA。
在前列腺癌细胞中,研究了 SN38-Snail siRNA CMD-壳聚糖纳米颗粒双重递药的理化特性、生长抑制特性和抗迁移能力。
我们的研究结果表明,在用 ChNP-CMD-SN38-siRNA 处理的细胞中,Snail 的 mRNA 水平分别在 24 小时和 48 小时后从 1.00 降至 0.30(±0.14)和 0.09(±0.04)。此外,E-钙黏蛋白和 Claudin-1 的倍数诱导分别从 1.00 增加至现在的 3.12(±0.62)、3.02(±0.28)(24 小时)和 5.6(±0.91)、4.42(±0.51)(48 小时)。此外,通过适当的纳米载体(壳聚糖纳米颗粒)共递送 SN38 和 Snail 特异性 siRNA 可以降低 PC-3 细胞的活力、增殖和迁移。
总之,封装 SN38 和 Snail 特异性 siRNA 的 ChNPs 可能作为治疗前列腺癌的有效抗癌药物递送系统具有巨大潜力。