Probing in vivo trafficking of polymer/DNA micellar nanoparticles using SPECT/CT imaging

Rajesh R. Patil, Jianhua Yu, Sangeeta R. Banerjee, Yong Ren, Derek Leong, Xuan Jiang, Martin Pomper, Benjamin Tsui, Dara L. Kraitchman, Hai Quan Mao

Research output: Contribution to journalArticle

Abstract

Successful translation of nonviral gene delivery to therapeutic applications requires detailed understanding of in vivo trafficking of the vehicles. This report compares the pharmacokinetic and biodistribution profiles of polyethylene glycol-b-polyphosphoramidate (PEG-b-PPA)/DNA micellar nanoparticles after administration through intravenous infusion, intrabiliary infusion, and hydrodynamic injection using single photon emission computed tomography/computed tomography (SPECT/CT) imaging. Nanoparticles were labeled with 111 In using an optimized protocol to retain their favorable physicochemical properties. Quantitative imaging analysis revealed different in vivo trafficking kinetics for PEG-b-PPA/DNA nanoparticles after different routes of administration. The intrabiliary infusion resulted in the highest liver uptake of micelles compared with the other two routes. Analysis of intrabiliary infusion by the two-compartment pharmacokinetic modeling revealed efficient retention of micelles in the liver and minimal micelle leakage from the liver to the blood stream. This study demonstrates the utility of SPECT/CT as an effective noninvasive imaging modality for the characterization of nanoparticle trafficking in vivo and confirms that intrabiliary infusion is an effective route for liver-targeted delivery of DNA-containing nanoparticles.

Original languageEnglish (US)
Pages (from-to)1626-1635
Number of pages10
JournalMolecular Therapy
Volume19
Issue number9
DOIs
StatePublished - Sep 2011

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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