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 language | English (US) |
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Pages (from-to) | 8573-8582 |
Number of pages | 10 |
Journal | ACS Nano |
Volume | 7 |
Issue number | 10 |
DOIs | |
State | Published - 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)