Multifunctional selenium nanoparticles: Chiral selectivity of delivering MDR-siRNA for reversal of multidrug resistance and real-time biofluorescence imaging

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• 作者：Qingchang Chen ; MS^a ; ¹ ; Qianqian Yu ; PhD^a ; ¹ ; Yanan Liu ; PhD^b ; Dhairya Bhavsar ; PhD^a ; Licong Yang ; PhD^a ; Xiaofan Ren ; BS^a ; Dongdong Sun ; PhD^a ; Wenjing Zheng ; MS^a ; Jie Liu ; PhD^a ; ^{tliuliu@jnu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Lan-mei Chen ; PhD^c
• 关键词：Chiral selenium nanoparticle ; Dinuclear ruthenium complexes ; Drug and gene delivery ; siRNA ; Multidrug resistance ; Biofluorescence imaging
• 刊名：Nanomedicine: Nanotechnology, Biology and Medicine
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：11
• 期：7
• 页码：1773-1784
• 全文大小：2215 K

文摘

Herein, 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 than 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 are promising vectors for the delivery of siRNA and for real-time tracking of treatment.

From the Clinical Editor

In this study, the authors designed bi-functional selenium nanoparticles with specific chirality to deliver siRNA, for targeting tumor MDR1 gene. The underlying ruthenium (II) complex could also offer fluorescence for real-time imaging. This new system has been shown to have enhanced efficacy against drug resistant tumor cells in both in-vitro and in-vivo experiments.