Flexible filaments for in vivo imaging and delivery: Persistent circulation of filomicelles opens the dosage window for sustained tumor shrinkage

David A. Christian, Shenshen Cai, Olga B. Garbuzenko, Takamasa Harada, Allison L. Zajac, Tamara Minko, Dennis E. Discher

Research output: Contribution to journalArticlepeer-review

207 Scopus citations

Abstract

Shape effects of synthetic carriers are largely unexplored in vivo, although recent findings suggest that flexible filaments can persist in the circulation even if microns in length. Here, to better assess biodistribution, a near-infrared fluorophore (NIRF) was incorporated into such block copolymer "filomicelles", and both in vivo and ex vivo imaging show that the majority of these wormlike micelles remain in the circulation for at least a day after intravenous injection. NIRF imaging further suggests that filomicelles convect into a tumor and some fragments can penetrate into the tumor stroma. To assess a functional effect, the hydrophobic drug paclitaxel (tax) was loaded into both filomicelles and sonication-generated spherical micelles of the same copolymer. Intravenous injection of tax-loaded filomicelles nearly doubles the maximum tolerated dose of tax in normal mice compared to tax-loaded spherical micelles. In tumor-bearing mice, the higher dose of tax produces greater and more sustained tumor shrinkage and tumor cell apoptosis. These results thus begin to address mechanisms for how nonspherical carriers deliver both imaging agents and anticancer therapeutics to solid tumors.

Original languageEnglish (US)
Pages (from-to)1343-1352
Number of pages10
JournalMolecular pharmaceutics
Volume6
Issue number5
DOIs
StatePublished - Oct 5 2009

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

Keywords

  • Block copolymer
  • Drug delivery
  • In vivo tracking
  • Near infrared
  • Optical imaging
  • Paclitaxel
  • Tumor
  • Worm micelle

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