Key Laboratory of Thin Film and Microfabrication (Ministry of Education), Department of Micro/Nano Electronics, School of Electronic Information and Electrical Engineering, Center of Hydrogen Science, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
Nanotechnology. 2020 Aug 14;31(33):335102. doi: 10.1088/1361-6528/ab8a8a. Epub 2020 Apr 17.
Dual-targeted therapy in HER2-positive breast cancer cells with the combination of carbon dots/HER3 siRNA and trastuzumab resulted in enhanced antitumor activity, which overcomes the resistance to trastuzumab monotherapy. Herein, we have developed branched polyethylenimine-functionalized carbon dot (BP-CD) nanocarriers, which exhibited efficient green fluorescent protein gene delivery and expression. The positively charged BP-CDs allowed for effective nucleic acid binding and displayed a highly efficient small interfering RNA (siRNA)-mediated delivery targeting of cancer cells. The transfection of BP-CDs and HER3 siRNA complexes down-regulated HER3 protein expression and induced significant cell growth inhibition in BT-474 cells. BP-CDs/HER3 siRNA complexes induced cell death of BT-474 cells through G0/G1 cell cycle arrest and apoptosis. The combined treatment of BP-CDs/HER3 siRNA complexes and trastuzumab caused greater cell growth suppression in BT-474 cells when compared to either agent alone. The findings suggest that this dual-targeted therapy with the combination of BP-CDs/HER3 siRNA and trastuzumab represents a promising approach in breast cancer.
双靶点治疗 HER2 阳性乳腺癌细胞，将碳点/HER3 siRNA 和曲妥珠单抗联合使用，可增强抗肿瘤活性，克服曲妥珠单抗单药治疗的耐药性。本研究制备了支化聚乙烯亚胺功能化碳点（BP-CD）纳米载体，该载体具有高效的绿色荧光蛋白基因传递和表达能力。带正电荷的 BP-CDs 可有效结合核酸，并对癌细胞进行高效的小干扰 RNA（siRNA）介导的靶向递送。BP-CDs 和 HER3 siRNA 复合物的转染可下调 HER3 蛋白表达，并显著抑制 BT-474 细胞的生长。BP-CDs/HER3 siRNA 复合物通过 G0/G1 细胞周期阻滞和细胞凋亡诱导 BT-474 细胞死亡。与单独使用任一药物相比，BP-CDs/HER3 siRNA 复合物与曲妥珠单抗联合使用对 BT-474 细胞的生长抑制作用更强。研究结果表明，这种联合 BP-CDs/HER3 siRNA 和曲妥珠单抗的双靶点治疗策略可能为乳腺癌的治疗提供新的思路。
