Vital microscopic analysis of polymeric micelle extravasation from tumor vessels: Macromolecular delivery according to tumor vascular growth stage

Katsuyoshi Hori, Masamichi Nishihara, Masayuki Yokoyama

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Particles larger than a specific size have been thought to extravasate from tumor vessels but not from normal vessels. Therefore, various nanoparticles incorporating anticancer drugs have been developed to realize selective drug delivery to solid tumors. However, it is not yet clear whether nanoparticles extravasate readily from all tumor vessels including vessels of microtumors. To answer this question, we synthesized new polymeric micelles labeled with fluorescein isothiocyanate (FITC) and injected them into the tail vein of rats with implanted skinfold transparent chambers. We also analyzed, by means of time-lapse vital microscopy with image analysis, extravasation of FITC micelles from tumor vessels at different stages of growth of Yoshida ascites sarcoma LY80. Polymeric micelles readily leaked from vessels at the interface between normal and tumor tissues and those at the interface between tumor tissues and necrotic areas. The micelles showed negligible extravasation, however, from the vascular network of microtumors less than 1mm in diameter and did not accumulate in the microtumor. Our results suggest that we must develop a novel therapeutic strategy that can deliver sufficient nanomedicine to microtumors.

Original languageEnglish
Pages (from-to)549-562
Number of pages14
JournalJournal of Pharmaceutical Sciences
Volume99
Issue number1
DOIs
Publication statusPublished - Jan 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

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