Hubei Province Key Laboratory of Coal Conversion and New Carbon Material, Wuhan University of Science and Technology, Wuhan 430081, China.
College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan 430081, China.
Colloids Surf B Biointerfaces. 2022 Jan;209(Pt 1):112203. doi: 10.1016/j.colsurfb.2021.112203. Epub 2021 Nov 14.
In order to obtain drug delivery carriers with good stability in blood and high cellular uptake efficiency, carboxyl groups and tertiary amine groups were respectively introduced into polyurethane to synthesize two kinds of amphiphilic polyurethanes with opposite charges (PUC and PUN). Their structures were characterized by Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (H NMR) spectroscopy and gel permeation chromatography (GPC). PUC-PUN co-assembled nanomicelles were prepared by electrostatic interaction between PUC and PUN micelles, which showed acid-sensitive property. When the pH of the solution was decreased from 7.4 to 6.5, PUC-PUN-1 micelles showed negative-to-positive charge-reversal property among these micelles. The results of stability and cell experiments demonstrated that PUC-PUN-1 micelles not only had excellent stability in simulated normal physiological environment but also could obviously enhance the cellular uptake efficiency. PUC-PUN-1 micelles had low cytotoxicity against SGC-7901 and MGC-803 cells, whereas PUC-PUN-1/DOX micelles had higher cytotoxicity compared to pure DOX and PUN-1/DOX micelles. Moreover, the results of in vivo antitumor activity experiments showed that PUC-PUN-1/DOX micelles had better tumor inhibition ability and safety than pure DOX. In addition, the results of in vitro drug release experiments indicated that PUC-PUN-1/DOX micelles had almost no burst release or leakage of drugs in pH 7.4 environment. However, the drug release was accelerated in pH 5.0, which followed Fickian diffusion mechanism.
为了获得在血液中具有良好稳定性和高细胞摄取效率的药物传递载体，分别将羧基和叔胺基团引入到聚氨酯中，合成了两种带有相反电荷的两亲性聚氨酯（PUC 和 PUN）。通过傅里叶变换红外光谱（FTIR）、核磁共振（H NMR）和凝胶渗透色谱（GPC）对其结构进行了表征。通过 PUC 和 PUN 胶束之间的静电相互作用制备了 PUC-PUN 共组装纳米胶束，其具有酸响应性。当溶液的 pH 值从 7.4 降低到 6.5 时，PUC-PUN-1 胶束表现出这些胶束之间的负到正电荷反转性质。稳定性和细胞实验结果表明，PUC-PUN-1 胶束不仅在模拟正常生理环境中具有优异的稳定性，而且还可以明显提高细胞摄取效率。与纯 DOX 和 PUN-1/DOX 胶束相比，PUC-PUN-1 胶束对 SGC-7901 和 MGC-803 细胞的毒性较低，而 PUC-PUN-1/DOX 胶束具有更高的细胞毒性。此外，体内抗肿瘤活性实验结果表明，与纯 DOX 相比，PUC-PUN-1/DOX 胶束具有更好的肿瘤抑制能力和安全性。此外，体外药物释放实验结果表明，在 pH7.4 环境中，PUC-PUN-1/DOX 胶束几乎没有药物的爆发释放或泄漏。然而，在 pH5.0 下，药物释放加速，遵循菲克扩散机制。
