Mohammad Gholinia Sarpoli Leila, Zare-Karizi Shohreh, Heidari Erfan, Hasanzadeh Akbar, Bayandori Mehrdad, Azedi Fereshteh, Hamblin Michael R, Karimi Mahdi
Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Department of Genetics, School of Biological Sciences, Varamin-Pishva Branch, Islamic Azad University, Varamin, Iran.
Pharm Dev Technol. 2022 Sep;27(7):785-793. doi: 10.1080/10837450.2022.2120003. Epub 2022 Sep 7.
Breast cancer is the second major cause of death worldwide among women. Co-delivery of anticancer drugs and nucleic acids targeting the apoptosis pathway could be a promising new approach.
In the present study, we synthesized a novel nanostructure for the co-delivery of curcumin and siRNA to breast cancer cells. Curcumin-loaded polylactic-co-glycolic acid (PLGA) was synthesized using an O/W emulsion-solvent diffusion method. It was coated with polyethylenimine (PEI) and subsequently complexed with Bcl-2 siRNA. Also, nanoparticles were characterized such as zeta potential, size distribution and drug encapsulation. Finally, the cytotoxicity of NP and Bcl-2 expression was evaluated.
The curcumin-loaded PLGA nanoparticles were 70 nm in size, and increased to 84 nm after incorporation of PEI plus Bcl-2 siRNA. The encapsulation ratio of the drug in our nanoparticle was 78%. Cellular internalization of PLGA-CUR-PEI/Bcl-2 siRNA NPs was confirmed by fluorescence microscopy with the broadcasting of the fluorescence in the cytoplasm and into the nucleus. The results of the cell viability assay revealed that curcumin-loaded PLGA coated with PEI and Bcl-2 siRNA exhibited the highest cytotoxicity against the T47D cell line, while the siRNA decreased the Bcl-2 expression by 90.7%.
The co-delivery of curcumin plus Bcl-2 siRNA with the PLGA-PEI nanosystem could be a synergistic drug carrier against breast cancer cells.
乳腺癌是全球女性第二大主要死因。联合递送抗癌药物和靶向凋亡途径的核酸可能是一种有前景的新方法。
在本研究中，我们合成了一种新型纳米结构，用于将姜黄素和小干扰RNA（siRNA）共同递送至乳腺癌细胞。采用水包油乳液-溶剂扩散法合成了负载姜黄素的聚乳酸-乙醇酸共聚物（PLGA）。用聚乙烯亚胺（PEI）对其进行包被，随后与Bcl-2 siRNA复合。此外，还对纳米颗粒的zeta电位、粒径分布和药物包封率等进行了表征。最后，评估了纳米颗粒的细胞毒性和Bcl-2表达。
负载姜黄素的PLGA纳米颗粒尺寸为70nm，加入PEI和Bcl-2 siRNA后增大至84nm。我们制备的纳米颗粒中药物的包封率为78%。通过荧光显微镜观察到PLGA-CUR-PEI/Bcl-2 siRNA纳米颗粒在细胞质和细胞核中均有荧光分布，证实了其细胞内化。细胞活力测定结果显示，负载姜黄素的PLGA经PEI和Bcl-2 siRNA包被后对T47D细胞系表现出最高的细胞毒性，而siRNA使Bcl-2表达降低了90.7%。
PLGA-PEI纳米系统联合递送姜黄素和Bcl-2 siRNA可能是一种针对乳腺癌细胞的协同药物载体。
