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Sci Rep. 2014 Jun 10;4:5232. doi: 10.1038/srep05232.

Quantity and accessibility for specific targeting of receptors in tumours.

Author information

1
1] Cancer Research Center, Sanford-Burnham Medical Research Institute, La Jolla, California 92037, USA [2] Center for Nanomedicine, and Department of Cell, Molecular and Developmental Biology, University of California Santa Barbara, Santa Barbara, CA 93106-9610, USA.
2
Department of Chemical Engineering, University of California Santa Barbara, Santa Barbara, CA 93106-5080, US.

Abstract

Synaphic (ligand-directed) targeting of drugs is an important potential new approach to drug delivery, particularly in oncology. Considerable success with this approach has been achieved in the treatment of blood-borne cancers, but the advances with solid tumours have been modest. Here, we have studied the number and availability for ligand binding of the receptors for two targeting ligands. The results show that both paucity of total receptors and their poor availability are major bottlenecks in drug targeting. A tumour-penetrating peptide greatly increases the availability of receptors by promoting transport of the drug to the extravascular tumour tissue, but the number of available receptors still remains low, severely limiting the utility of the approach. Our results emphasize the importance of using drugs with high specific activity to avoid exceeding receptor capacity because any excess drug conjugate would lose the targeting advantage. The mathematical models we describe make it possible to focus on those aspects of the targeting mechanism that are most likely to have a substantial effect on the overall efficacy of the targeting.

PMID:
24912981
PMCID:
PMC4050384
DOI:
10.1038/srep05232
[Indexed for MEDLINE]
Free PMC Article
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