Affordable Access

deepdyve-link
Publisher Website

Quantity and accessibility for specific targeting of receptors in tumours.

Authors
Type
Published Article
Journal
Scientific Reports
Publisher
Springer Nature
Volume
4
Pages
5232–5232
Identifiers
DOI: 10.1038/srep05232
Source
Ruoslahti Lab
License
Unknown

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.

Report this publication

Statistics

Seen <100 times