School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China.
School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China.
Bioorg Med Chem. 2022 Sep 1;69:116884. doi: 10.1016/j.bmc.2022.116884. Epub 2022 Jun 13.
Protein kinase N3 (PKN3), an AGC-family member, is often overexpressed in breast tumor cells. RNAi therapy is a promising approach to inhibit tumor growth by reducing the expression of PKN3. In this report, lipid nanoparticles encapsulated with new shRNA PKN3 (SS-LNP/shPKN3) with redox-responsiveness were developed in order to specifically down-regulate the expression of PKN3 for breast cancer treatment. The SS-LNP/shPKN3 was prepared by microfluidic method using disulfide bonds based ionizable lipid as main component. The as-prepared SS-LNP/shPKN3 lipid nanoparticles were characterized via using dynamic light scattering (DLS) and transmission electron microscopy (TEM). The results indicated that the obtained SS-LNP/shPKN3 exhibited uniform particle size and regular spherical morphology. Moreover, glutathione (GSH) triggered release of shPKN3 confirmed the redox-responsiveness of the SS-LNP/shPKN3. Finally, the anti-tumor effect of SS-LNP/shPKN3 was evaluated against MDA-MB-231 cells and derived xenograft tumor bearing mice. It was found that the SS-LNP/shPKN3-2 had the highest PKN3 protein inhibition rate of 60.8% and tumor inhibition rate of 62.3%. Taken together, the SS-LNP/shPKN3 might be a potential therapeutic strategy for breast cancer.
蛋白激酶 N3（PKN3）是 AGC 家族的成员，在乳腺癌细胞中常过表达。RNAi 疗法是通过降低 PKN3 的表达来抑制肿瘤生长的一种很有前途的方法。在本报告中，开发了具有氧化还原响应性的新型 shRNA PKN3（SS-LNP/shPKN3）包封的脂质纳米颗粒，以专门下调 PKN3 的表达用于乳腺癌治疗。SS-LNP/shPKN3 通过使用基于二硫键的可离子化脂质作为主要成分的微流控方法制备。通过动态光散射（DLS）和透射电子显微镜（TEM）对所制备的 SS-LNP/shPKN3 脂质纳米颗粒进行了表征。结果表明，所得到的 SS-LNP/shPKN3 表现出均匀的粒径和规则的球形形态。此外，谷胱甘肽（GSH）触发 shPKN3 的释放证实了 SS-LNP/shPKN3 的氧化还原响应性。最后，评估了 SS-LNP/shPKN3 对 MDA-MB-231 细胞和衍生的异种移植肿瘤荷瘤小鼠的抗肿瘤作用。结果发现，SS-LNP/shPKN3-2 具有最高的 PKN3 蛋白抑制率 60.8%和肿瘤抑制率 62.3%。综上所述，SS-LNP/shPKN3 可能是一种治疗乳腺癌的潜在治疗策略。
