Quantity and accessibility for specific targeting of receptors in tumours.

TitleQuantity and accessibility for specific targeting of receptors in tumours.
Publication TypeJournal Article
Year of Publication2014
AuthorsHussain S, Rodriguez-Fernandez M, Braun GB, Doyle FJ, Ruoslahti E
JournalSci Rep
Volume4
Pagination5232
Date Published2014
ISSN2045-2322
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.

DOI10.1038/srep05232
Alternate JournalSci Rep
PubMed ID24912981
PubMed Central IDPMC4050384
Grant ListCA152327 / CA / NCI NIH HHS / United States
CA30199 / CA / NCI NIH HHS / United States
P30 CA030199 / CA / NCI NIH HHS / United States
R01 CA152327 / CA / NCI NIH HHS / United States
T32 CA121949 / CA / NCI NIH HHS / United States