siRNA-Loaded Hydroxyapatite Nanoparticles for <i>KRAS</i> Gene Silencing in Anti-Pancreatic Cancer Therapy

Pancreatic carcinoma (PC) is greatly induced by the <i>KRAS</i> 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, th...

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Main Authors: Dandan Luo (Author), Xiaochun Xu (Author), M. Zubair Iqbal (Author), Qingwei Zhao (Author), Ruibo Zhao (Author), Jabeen Farheen (Author), Quan Zhang (Author), Peiliang Zhang (Author), Xiangdong Kong (Author)
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Published: MDPI AG, 2021-09-01T00:00:00Z.
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001 doaj_1d0d8ec58a1e4b6abdba89dd8eba82f2
042 |a dc 
100 1 0 |a Dandan Luo  |e author 
700 1 0 |a Xiaochun Xu  |e author 
700 1 0 |a M. Zubair Iqbal  |e author 
700 1 0 |a Qingwei Zhao  |e author 
700 1 0 |a Ruibo Zhao  |e author 
700 1 0 |a Jabeen Farheen  |e author 
700 1 0 |a Quan Zhang  |e author 
700 1 0 |a Peiliang Zhang  |e author 
700 1 0 |a Xiangdong Kong  |e author 
245 0 0 |a siRNA-Loaded Hydroxyapatite Nanoparticles for <i>KRAS</i> Gene Silencing in Anti-Pancreatic Cancer Therapy 
260 |b MDPI AG,   |c 2021-09-01T00:00:00Z. 
500 |a 10.3390/pharmaceutics13091428 
500 |a 1999-4923 
520 |a Pancreatic carcinoma (PC) is greatly induced by the <i>KRAS</i> 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 <i>KRAS</i> 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 <i>KRAS</i> 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. 
546 |a EN 
690 |a hydroxyapatite 
690 |a siRNA delivery 
690 |a pancreatic cancer cells 
690 |a <i>KRAS</i> gene 
690 |a gene silence 
690 |a anticancer 
690 |a Pharmacy and materia medica 
690 |a RS1-441 
655 7 |a article  |2 local 
786 0 |n Pharmaceutics, Vol 13, Iss 9, p 1428 (2021) 
787 0 |n https://www.mdpi.com/1999-4923/13/9/1428 
787 0 |n https://doaj.org/toc/1999-4923 
856 4 1 |u https://doaj.org/article/1d0d8ec58a1e4b6abdba89dd8eba82f2  |z Connect to this object online.