Ganesh, S, Iyer, AK, Gattacceca, F, Morrissey, DV and Amiji, MM (2013) In vivo biodistribution of siRNA and cisplatin administered using CD44-targeted hyaluronic acid nanoparticles. JOURNAL OF CONTROLLED RELEASE. pp. 699-706.

Abstract

Multidrug resistance (MDR) is a significant problem in the clinical management of several cancers. Overcoming MDR generally involves multi-modal therapeutic approaches that integrate enhancement of delivery efficiency using targeted nano-platforms as well as strategies that can sensitize cancer cells to drug treatments. We recently demonstrated that tandem delivery of siRNAs that downregulate anti-apoptotic genes overexpressed in cisplatin resistant tumors followed by therapeutic challenge using cisplatin loaded CD44 targeted hyaluronic acid (HA) nanoparticle (NP) induced synergistic antitumor response CD44 expressing tumors that are resistant to cisplatin. In the current study, a near infrared (NIR) dye-loaded HA NP was employed to image the whole body localization of NPs after intravenous (i.v.) injection into live mice bearing human lung tumors that were sensitive and resistant to cisplatin. In addition, we quantified the siRNA duplexes and cisplatin dose distribution in various tissues and organs using an ultra-sensitive quantitative PCR method and inductively coupled plasma-mass spectrometry (ICP-MS), respectively, after i.v. injection of the payload loaded HA NPs in tumor bearing mice. Our findings demonstrate that the distribution pattern of the siRNA and cisplatin using specifically engineered CD44 targeting HA NPs correlated well with the tumor targeting capability as well as the activity and efficacy obtained with combination treatments. (C) 2013 Elsevier B.V. All rights reserved

Item Type:	Article
Additional Information:	pubid: 120 nvp_institute: NIBR contributor_address: Northeastern Univ, Dept Pharmaceut Sci, Sch Pharm, Bouve Coll Hlth Sci, Boston, MA 02115 USA, Novartis Inst Biomed Res Inc, Cambridge, MA 02139 USA ; Northeastern Univ, Dept Pharmaceut Sci, Sch Pharm, Bouve Coll Hlth Sci, Boston, MA 02115 USA m.amiji@neu.edu; Northeastern Univ, Dept Pharmaceut Sci, Sch Pharm, Bouve Coll Hlth Sci, Boston, MA 02115 USA, Univ Montpellier I, Dept Pharmacokinet, Fac Pharm, EA4215, F-34093 Montpellier 5, France ; Novartis Inst Biomed Res Inc, Cambridge, MA 02139 USA ; Northeastern Univ, Dept Pharmaceut Sci, Sch Pharm, Bouve Coll Hlth Sci, Boston, MA 02115 USA; Novartis Inst Biomed Res Inc, Cambridge, MA 02139 USA; Amiji, M M; Northeastern Univ, Dept Pharmaceut Sci, Sch Pharm, Bouve Coll Hlth Sci, Boston, MA 02115 USA
Date Deposited:	13 Oct 2015 13:13
Last Modified:	13 Oct 2015 13:13
URI:	https://oak.novartis.com/id/eprint/21957