title: Biodistribution and Pharmacokinetics Study of siRNA-loaded Anti-NTSR1-mAb-functionalized Novel Hybrid Nanoparticles in a Metastatic Orthotopic Murine Lung Cancer Model.
abstract: Small interfering RNA (siRNA) is effective in silencing critical molecular pathways in cancer. The use of this tool as a treatment modality is limited by lack of an intelligent carrier system to enhance the preferential delivery of this molecule to specific targets in vivo. In the present study, the in vivo behavior of novel anti-NTSR1-mAb-functionalized antimutant K-ras siRNA-loaded hybrid nanoparticles, delivered by i.p. injection to non-small-cell lung cancer in mice models, was investigated and compared to that of a naked siRNA formulation. The siRNA in anti-NTSR1-mAb-functionalized hybrid nanoparticles was preferentially accumulated in tumor-bearing lungs and metastasized tumor for at least 48 hours while the naked siRNA formulation showed lack of preferential accumulation in all of the organs monitored. The plasma terminal half-life of nanoparticle-delivered siRNA was 11 times higher (17-1.5 hours) than that of the naked siRNA formulation. The mean residence time and AUClast were 3.4 and 33 times higher than the corresponding naked siRNA formulation, respectively. High-performance liquid chromatography analysis showed that the hybrid nanoparticle carrier system protected the encapsulated siRNA against degradation in vivo. Our novel anti-NTSR1-mAb-functionalized hybrid nanoparticles provide a useful platform for in vivo targeting of siRNA for both experimental and clinical purposes.
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Maryna
authors.initials: M
authors.lastname: Perepelyuk
authors.affiliation: Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Chellappagounder
authors.initials: C
authors.lastname: Thangavel
authors.affiliation: Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Den
authors.affiliation: Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Lu
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Adam E
authors.initials: AE
authors.lastname: Snook
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Sunday A
authors.initials: SA
authors.lastname: Shoyele
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