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Highly efficient Gab2 siRNA delivery to ovarian cancer cells mediated by chitosan-polyethyleneimine nanoparticles
Lei Wang1, Weimin Wu, Jingshuai Wang
1Department of Obstetrics and Gynaecology, Tongji Hospital of Tongji University, Tongji University School of Medicine, Shanghai 200065, China. jjwang0524@sina.com.
Abstract:
Malignant bowel obstruction (MBO) is a serious complication which causes high death rate and low quality of life (QOL) for patients diagnosed at an advanced stage of ovarian cancer. RNA interference (RNAi) could be a promising method for the treatment of ovarian cancer and could decrease the morbidity of MBO. Gab2 gene is overexpressed in ovarian cancer compared with normal ovarian tissue, and regulates the migratory behaviors and E-cadherin expression via activation of the PI3K pathway in ovarian cancer cells. Here, chitosan-polyethyleneimine (PEI, Mw 1800) copolymer nanoparticles were synthesized as nanocarriers to deliver Gab2 siRNA into SKOV3 cells. The silencing effects against the Gab2 gene and the antitumor effects by the chitosan-PEI-Gab2 siRNA nanoparticles (chitosan-PEI-Gab2 NPs) were studied. Results showed that highly efficient silencing effects against Gab2 expression and its downstream effector, AKT protein, at more than 90% deregulation were obtained by chitosan-PEI NP mediated Gab2 siRNA delivery, so as to exhibit obvious antitumor effects against SKOV3 cells with low cytotoxicity, and induce cell apoptosis in early and late stages. The study will provide novel strategies to overcome MBO in ovarian cancer by the efficient knockdown of Gab2 expression.
Insights
This study developed chitosan-polyethyleneimine nanoparticles to deliver Gab2 siRNA, effectively silencing the Gab2 gene in ovarian cancer cells. This approach shows promise for treating malignant bowel obstruction and improving ovarian cancer patient quality of life.
Area of Science:
- Biomedical Engineering
- Cancer Research
- Nanotechnology
Background:
- Malignant bowel obstruction (MBO) significantly impacts advanced ovarian cancer patients' quality of life (QOL).
- Gab2 gene overexpression in ovarian cancer drives cell migration and is linked to MBO.
- RNA interference (RNAi) offers a potential therapeutic strategy for ovarian cancer and MBO.
Purpose of the Study:
- To synthesize chitosan-polyethyleneimine (PEI) copolymer nanoparticles for delivering Gab2 siRNA.
- To evaluate the efficacy of these nanoparticles in silencing Gab2 expression in SKOV3 ovarian cancer cells.
- To assess the potential of Gab2 knockdown in treating MBO associated with ovarian cancer.
Main Methods:
- Chitosan-PEI (Mw 1800) copolymer nanoparticles were synthesized as nanocarriers.
- Gab2 siRNA was delivered into SKOV3 cells using these nanoparticles.
- Gene silencing effects on Gab2 and its downstream effector AKT were quantified.
- Antitumor effects and cytotoxicity of the nanoparticles were evaluated.
Main Results:
- Chitosan-PEI nanoparticles efficiently delivered Gab2 siRNA, achieving over 90% deregulation of Gab2 and AKT.
- Significant antitumor effects were observed in SKOV3 cells with low cytotoxicity.
- The treatment induced apoptosis in both early and late stages of cancer cells.
Conclusions:
- Chitosan-PEI nanoparticle-mediated Gab2 siRNA delivery is effective in silencing Gab2 expression in ovarian cancer cells.
- This approach demonstrates potent antitumor activity and induces apoptosis.
- Gab2 knockdown presents a novel therapeutic strategy for overcoming MBO in advanced ovarian cancer.
