Therapeutic silencing of mTOR by systemically administered siRNA-loaded neutral liposomal nanoparticles inhibits DMBA-induced mammary carcinogenesis

Menée in vitro et in vivo, cette étude met en évidence l'intérêt thérapeutique de nanoparticules liposomales chargées en petits ARNs interférents ciblant l'expression de mTOR pour inhiber la carcinogenèse mammaire et la croissance tumorale

Résumé en anglais

Background : Mammary carcinogenesis possesses great challenges due to the lack of effectiveness of the multiple therapeutic options available. Gene therapy-based cancer treatment strategy provides more targeting accuracy, fewer side effects, and higher therapeutic efficiency. Downregulation of the oncogene mTOR by mTOR-siRNA is an encouraging approach to reduce cancer progression. However, its employment as means of therapeutic strategy has been restricted due to the unavailability of a suitable delivery system.

Methods : A suitable nanocarrier system made up of 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) has been developed to prevent degradation and for proficient delivery of siRNA. This was followed by in vitro and in vivo anti-breast cancer efficiency analysis of the mTOR siRNA-loaded neutral liposomal formulation (NL-mTOR-siRNA).

Results : In our experiment, a profound reduction in MCF-7 cell growth, proliferation and invasion was ascertained following extensive downregulation of mTOR expression. NL-mTOR-siRNA suppressed tumour growth and restored morphological alterations of DMBA-induced breast cancer. In addition, neutral liposome enhanced accumulation of siRNA in mammary cancer tissues facilitating its deep cytosolic distribution within the tumour, which allows apoptosis thereby facilitating its anti-tumour potential.

Conclusion : Hence, the current study highlighted the augmented ground for therapies aiming toward cancerous cells to diminish mTOR expression by RNAi in managing mammary carcinoma.