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Enhanced delivery of monomethoxypoly(ethylene glycol)‐poly(lactic‐co‐glycolic acid)‐poly l ‐lysine nanoparticles loading platelet‐derived growth factor BB small interfering RNA by ultrasound and/or microbubbles to rat retinal pigment epithelium cells
Author(s) -
Du Jing,
Shi Qiu Sheng,
Sun Ying,
Liu Pei Feng,
Zhu Ming Jie,
Du Lian Fang,
Duan You Rong
Publication year - 2011
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.1574
Subject(s) - small interfering rna , plga , ethylene glycol , glycolic acid , chemistry , flow cytometry , growth factor , microbubbles , biophysics , viability assay , nanoparticle , lactic acid , gene silencing , microbiology and biotechnology , rna , materials science , biochemistry , cell , nanotechnology , ultrasound , receptor , biology , medicine , organic chemistry , genetics , radiology , bacteria , gene
Background A novel small interfering RNA (siRNA) delivery method based on the combined use of nanoparticles (NPs) with ultrasound (US) and/or microbubbles (MBs) was introduced in the present study. We investigated the efficacy and safety of US and/or MBs‐enhanced delivery of monomethoxypoly(ethylene glycol)‐poly(lactic‐co‐glycolic acid)‐poly l ‐lysine (mPEG‐PLGA‐PLL) NPs loading platelet‐derived growth factor BB (PDGF‐BB) siRNA to rat retinal pigment epithelium (RPE)‐J cells. Methods The effect of US and/or MBs on the delivery of NPs containing Cy3‐labeled siRNA was evaluated by fluorescence microscopy and flow cytometry. Potential toxicity of NPs and cell viability under different conditions of US and/or MBs were assessed by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide method. Results The results obtained showed that low intensity US or 15–20% MBs could increase the delivery efficiency of a lower concentration of mPEG‐PLGA‐PLL NPs loading siRNA to RPE‐J cells, whereas the combination of US with MBs under the optimal conditions for the enhancement of NPs delivery did not further increase the cellular uptake of NPs compared to either US or MBs alone ( p = 0.072 and p = 0.488, respectively). Under the optimal condition for US‐enhanced NPs delivery, the enhanced PDGF‐BB gene silencing with a combination of US and NPs encapsulating siRNA resulted in a significant decrease of mRNA and protein expression levels compared to NPs alone. Conclusions US and/or MBs could be used safely to enhance the delivery of NPs loading siRNA to rat RPE‐J cells. A combination of the chemical (mPEG‐PLGA‐PLL NPs loading siRNA) and physical (US) approaches could more effectively downregulate the mRNA and protein expression of PDGF‐BB. Copyright © 2011 John Wiley & Sons, Ltd.