Serum Proteins as Drug Carriers of Anticancer Agents: A Review

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Abstract
Targeted delivery of anticancer drugs is one of the most actively pursued goals in anticancer chemotherapy. Serum proteins such as transferrin, albumin, and low-density lipoprotein (LDL) offer promise for the selective delivery of antineoplastic agents due to their accumulation in tumor tissue. Uptake of these proteins in solid tumors is mediated by a number of factors, including an increased metabolic activity of tumors, an enhanced vascular permeability of tumor blood vessels for circulating macromolecules, and a lack of a functional lymphatic drainage system in tumor tissue. At the tumor site, transferrin, low-density lipoprotein, and albumin are taken up by the tumor cell through receptor-mediated and fluid phase endocytosis, respectively. Serum protein conjugates can be designed to release the bound antitumor drug after cellular uptake of the drug conjugate. This review covers the diagnostic evidence for tumor accumulation of serum proteins and the design, development, and biological evaluation of drug conjugates with transferrin, albumin, and low-density lipoprotein.