Toward a magic or imaginary bullet? Ligands for drug targeting to cancer cells: principles, hopes, and challenges.
There are many problems directly correlated with the systemic administration of drugs and how they reach their target site. Targeting promises to be a hopeful strategy as an improved means of drug delivery, with reduced toxicity and minimal adverse side effects. Targeting exploits the high affinity of cell-surface-targeted ligands, either directly or as carriers for a drug, for specific retention and uptake by the targeted diseased cells. One of the most important parameters which should be taken into consideration in the selection of an appropriate ligand for targeting is the binding affinity (K D). In this review we focus on the importance of binding affinities of monoclonal antibodies, antibody derivatives, peptides, aptamers, DARPins, and small targeting molecules in the process of selection of the most suitable ligand for targeting of nanoparticles. In order to provide a critical comparison between these various options, we have also assessed each technology format across a range of parameters such as molecular size, immunogenicity, costs of production, clinical profiles, and examples of the level of selectivity and toxicity of each. Wherever possible, we have also assessed how incorporating such a targeted approach compares with, or is superior to, original treatments.
Laboratory of Cytobiochemistry, Faculty of Biotechnology, University of Wrocław, Wrocław, Poland.
Monika
M
Toporkiewicz
Laboratory of Cytobiochemistry, Faculty of Biotechnology, University of Wrocław, Wrocław, Poland.
Justyna
J
Meissner
Laboratory of Cytobiochemistry, Faculty of Biotechnology, University of Wrocław, Wrocław, Poland.
Lucyna
L
Matusewicz
Laboratory of Cytobiochemistry, Faculty of Biotechnology, University of Wrocław, Wrocław, Poland.
Aleksander
A
Czogalla
Laboratory of Cytobiochemistry, Faculty of Biotechnology, University of Wrocław, Wrocław, Poland.
Aleksander F
AF
Sikorski
D000970:Antineoplastic Agents; D016503:Drug Delivery Systems; D006801:Humans; D008024:Ligands; D053758:Nanoparticles
D000970:Antineoplastic Agents; D008024:Ligands
EGFR; cancer; drug delivery; monoclonal antibody; targeting; tumor