Effect of folate-targeted nanoparticle size on their rates of penetration into solid tumors

Erina Vlashi, Lindsay E. Kelderhouse, Jennifer E. Sturgis, Philip Low

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

Targeted therapies are emerging as a preferred strategy for the treatment of cancer and other diseases. To evaluate the impact of a high affinity targeting ligand on the rate and extent of tumor penetration of different sized nanomedicines, we have used intravital multiphoton microscopy to quantitate the kinetics of tumor accumulation of a homologous series of folate-PEG-rhodamine conjugates prepared with polyethylene glycols (PEG) of different molecular weights. We demonstrate that increasing the size of the folate-PEG-rhodamine conjugates results in both longer circulation times and slower tumor penetration rates. Although a "binding site barrier" is observed with the folate-linked polymers in folate receptor expressing tumors, ligand targeting eventually leads to increased tumor accumulation, with endocytosis of the targeted nanocarriers contributing to their enhanced tumor retention. Because the effects of nanocarrier size, shape, chemistry, and targeting ligand are interconnected and complex, we suggest that these parameters must be carefully optimized for each nanocarrier to ensure optimal drug delivery in vivo.

Original languageEnglish (US)
Pages (from-to)8573-8582
Number of pages10
JournalACS Nano
Volume7
Issue number10
DOIs
StatePublished - Oct 22 2013

Keywords

  • binding site barrier
  • folate receptor
  • intravital multiphoton microscopy
  • nanomedicines size
  • tumor accumulation

ASJC Scopus subject areas

  • Engineering(all)
  • Materials Science(all)
  • Physics and Astronomy(all)

Fingerprint Dive into the research topics of 'Effect of folate-targeted nanoparticle size on their rates of penetration into solid tumors'. Together they form a unique fingerprint.

Cite this