Capillary-wall collagen as a biophysical marker of nanotherapeutic permeability into the tumor microenvironment

Kenji Yokoi, Milos Kojic, Miljan Milosevic, Tomonori Tanei, Mauro Ferrari, Arturas Ziemys

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

The capillary wall is the chief barrier to tissue entry of therapeutic nanoparticles, thereby dictating their efficacy. Collagen fibers are an important component of capillary walls, affecting leakiness in healthy or tumor vasculature. Using a computational model along with in vivo systems, we compared how collagen structure affects the diffusion flux of a 1-nm chemotherapeutic molecule [doxorubicin (DOX)] and an 80-nm chemotherapy-loaded pegylated liposome (DOX-PLD) in tumor vasculature. We found a direct correlation between the collagen content around a tumor vessel to the permeability of that vessel permeability to DOX-PLD, indicating that collagen content may offer a biophysical marker of extravasation potential of liposomal drug formulations. Our results also suggested that while pharmacokinetics determined the delivery of DOX and DOX-PLD to the same tumor phenotype, collagen content determined the extravasation of DOX-PLD to different tumor phenotypes. Transport physics may provide a deeper viewinto hownanotherapeutics cross biological barriers, possibly helping explain the balance between biological and physical aspects of drug delivery.

Original languageEnglish (US)
Pages (from-to)4239-4246
Number of pages8
JournalCancer research
Volume74
Issue number16
DOIs
StatePublished - Aug 15 2014

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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