Intracellular trafficking considerations in the development of natural ligand-drug molecular conjugates for cancer.

Dennis J Yoon, Christina T Liu, Devin S Quinlan, Parsa M Nafisi, Daniel T Kamei

Journal: Annals of biomedical engineering 2011;39(4):1235-51

PMID: 21350890

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Abstract

Overexpressed receptors, characteristic of many cancers, have been targeted by various researchers to achieve a more specific treatment for cancer. A common approach is to use the natural ligand for the overexpressed receptor as a cancer-targeting agent which can deliver a chemically or genetically conjugated toxic molecule. However, it has been found that the therapeutic efficacy of such ligand-drug molecular conjugates can be limited, since they naturally follow the intracellular trafficking pathways of the endogenous ligands. Therefore, a thorough understanding of the intracellular trafficking properties of these ligands can lead to novel design criteria for engineering ligands to be more effective drug carriers. This review presents a few commonly used ligand/receptor systems where intracellular trafficking considerations can potentially improve the therapeutic efficacy of the ligand-drug molecular conjugates.

Address: Department of Bioengineering, University of California-Los Angeles, CA 90095, USA.

DOI: 10.1007/s10439-011-0280-y

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https://doi.org/10.1007/s10439-011-0280-y

MeSH Terms: Antineoplastic Agents, Biological Transport, Active, Biomedical Engineering, Diphtheria Toxin, Doxorubicin, Drug Carriers, Epidermal Growth Factor, ErbB Receptors, Exotoxins, Folic Acid, Folic Acid Transporters, Humans, Interleukin-13, Ligands, Models, Biological, Neoplasms, Receptors, Interleukin-13, Receptors, Transferrin, Ricin, Signal Transduction, Transferrin, Transforming Growth Factor alpha