Multifunctional Selenium Nanoparticles: Chiral Selectivity of Delivering MDR-siRNA for Reversal of Multidrug Resistance and Real-time Biofluorescence Imaging

Publication date: Available online 8 May 2015 Source:Nanomedicine: Nanotechnology, Biology and Medicine Author(s): Qingchang Chen , Qianqian Yu , Yanan Liu , Dhairya Bhavsar , Licong Yang , Xiaofan Ren , Dongdong Sun , Wenjing Zheng , Jie Liu , Lan-mei Chen In this paper, chiral selenium nanoparticles (L-SeNPs/D-SeNPs) modified with a dinuclear Ruthenium (II) complex were used to effectively deliver siRNA targeting the MDR1 gene. In this co-delivery system, the luminescent dinuclear Ruthenium (II) complex was developed to act as a gene carrier and anti-tumor drug, while offering luminescent imaging to follow the intracellular trafficking. Interestingly, Ru@L-SeNPs exhibited a stronger protein and pDNA affinity then Ru@D-SeNPs, indicating that chirality may have an effect on pDNA/siRNA binding and biocompatibility. Cisplatin-resistant A549R cells treated with Ru@L-SeNPs-siRNA demonstrated significant downregulation of P-glycoprotein (P-gp) expression, resulting in unprecedented enhanced cytotoxicity through the induction of apoptosis with the involvement of phosphorylation of p53, MAPK and PI3K/Akt signaling pathways. In vivo investigation confirmed that Ru@L-SeNPs-siRNA nanoparticles exhibited high tumor-targeted fluorescence, enhanced anti-tumor efficacy, and decreased systemic toxicity. These results suggest that Ru@L-SeNPs is a promising vector for the delivery of siRNA and for real-time tracking of treatment. Graphical abstract
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research