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- Title
Systemic delivery of siRNA via LCP nanoparticle efficiently inhibits lung metastasis.
- Authors
Yang, Yang; Li, Jun; Liu, Feng; Huang, Leaf
- Abstract
Targeted delivery remains the major challenge for the application of small interfering RNA (siRNA). We have developed a lipid/calcium/phosphate (LCP) nanoparticle (NP) to improve siRNA delivery efficiency. The LCP NP was prepared by using microemulsion technology to form calcium/phosphate (CaP) core and further coated with cationic lipids. The final NP was grafted with polyethylene glycol (PEG) and anisamide (AA) ligand on the surface to target sigma receptor-expressing B16F10 melanoma cells. The LCP NP exhibited a 40 nm particle size, a +25 mV zeta-potential, and 91% siRNA encapsulation efficiency. After a single intravenous (i.v.) injection of antiluciferase siRNA (0.12 mg siRNA/kg) formulated in targeted LCP NP, luciferase activity in metastatic B16F10 tumor-loaded lungs decreased by 78% in C57BL/6 mice. In a therapeutic experiment, siRNA against MDM2, c-myc, and VEGF coformulated in the targeted LCP NP resulted in simultaneous silencing of the respective oncogenes in metastatic nodules. Treatment with siRNA in the targeted NP significantly reduced lung metastases (~70-80%) at a relatively low dose (0.36 mg/kg), whereas control group showed little therapeutic effect. Moreover, this targeted LCP NP significantly prolonged the mean survival time of the animals by 27.8% compared to control group without showing any toxicity at the therapeutic dose.
- Publication
Molecular therapy : the journal of the American Society of Gene Therapy, 2012, Vol 20, Issue 3, p609
- ISSN
1525-0024
- Publication type
Journal Article
- DOI
10.1038/mt.2011.270