siRNA-Loaded Hydroxyapatite Nanoparticles for KRAS Gene Silencing in Anti-Pancreatic Cancer Therapy

• Published in: Pharmaceutics Vol. 13; no. 9; p. 1428
• Main Authors: Luo, Dandan, Xu, Xiaochun, Iqbal, M. Zubair, Zhao, Qingwei, Zhao, Ruibo, Farheen, Jabeen, Zhang, Quan, Zhang, Peiliang, Kong, Xiangdong
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 08.09.2021; MDPI
• Subjects: anticancer; Apoptosis; Biocompatibility; Cancer therapies; Chemotherapy; Cyclin-dependent kinases; Cytotoxicity; gene silence; Hydroxyapatite; Kinases; KRAS gene; Morphology; Mortality; Mutation; Nanoparticles; Pancreatic cancer; pancreatic cancer cells; Polyethylene glycol; Proteins; siRNA delivery; Spectrum analysis; Tissue engineering; Tumors; China
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics13091428

Pancreatic carcinoma (PC) is greatly induced by the KRAS gene mutation, but effective targeted delivery for gene therapy has not existed. Small interfering ribonucleic acid (siRNA) serves as an advanced therapeutic modality and holds great promise for cancer treatment. However, the development of a non-toxic and high-efficiency carrier system to accurately deliver siRNA into cells for siRNA-targeted gene silencing is still a prodigious challenge. Herein, polyethylenimine (PEI)-modified hydroxyapatite (HAp) nanoparticles (HAp-PEI) were fabricated. The siRNA of the KRAS gene (siKras) was loaded onto the surface of HAp-PEI via electrostatic interaction between siRNA and PEI to design the functionalized HAp-PEI nanoparticle (HAp-PEI/siKras). The HAp-PEI/siKras was internalized into the human PC cells PANC-1 to achieve the maximum transfection efficiency for active tumor targeting. HAp-PEI/siKras effectively knocked down the expression of the KRAS gene and downregulated the expression of the Kras protein in vitro. Furthermore, the treatment with HAp-PEI/siKras resulted in greater anti-PC cells’ (PANC-1, BXPC-3, and CFPAC-1) efficacy in vitro. Additionally, the HAp-PEI exhibited no obvious in vitro cytotoxicity in normal pancreatic HPDE6-C7 cells. These findings provided a promising alternative for the therapeutic route of siRNA-targeted gene engineering for anti-pancreatic cancer therapy.