Nanolipoparticles-mediated MDR1 siRNA delivery reduces doxorubicin resistance in breast cancer cells and silences MDR1 expression in xenograft model of human breast cancer

摘要: Objective(s): P-glycoprotein (P-gp) is an efflux protein, the overexpression of which has been associated with multidrug resistance in various cancers. Although siRNA delivery to reverse P-gp expression may be promising for sensitizing tumor cells cytotoxic drugs, therapeutic use requires effective carriers that can deliver intracellularly minimal toxicity on target cells. We investigated a special class PEGylated lipid-based nanoparticles (NP), named nanolipoparticles (NLPs), siRNA-mediated downregulation. Materials and Methods: NLPs were prepared based low detergent dialysis method. After characterization, we evaluated effect delivery, downregulation compared oligofectamineTM (OFA) vitro vivo. Results: Our results showed significant decrease subsequent enhancement chemosensitivity doxorubicin vitro. effectiveness OFA was limited, vivo studies noticeable systemic delivery. using could downregulate MDR1 more than 80%, while had vivo. Conclusion: The indicated suitable systems therapy.