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Toward a magic or imaginary bullet? Ligands for drug targeting to cancer cells: principles, hopes, and challenges

Authors Toporkiewicz M, Meissner J, Matusewicz L, Czogalla A, Sikorski AF,

Received 18 September 2014

Accepted for publication 26 November 2014

Published 17 February 2015 Volume 2015:10(1) Pages 1399—1414

DOI https://doi.org/10.2147/IJN.S74514

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Thomas J Webster

Monika Toporkiewicz, Justyna Meissner, Lucyna Matusewicz, Aleksander Czogalla, Aleksander F Sikorski

Laboratory of Cytobiochemistry, Faculty of Biotechnology, University of Wrocław, Wrocław, Poland

Abstract: 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 (KD). 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.

Keywords: targeting, drug delivery, tumor, monoclonal antibody, EGFR, cancer

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