Cancer Drug Delivery by Serum Proteins.

      Аннотация: Targeted delivery of anticancer drugs in vivo remains a major challenge. Serum proteins are emerging as potential carriers for drug delivery. In this book, the loading efficacies of anticancer drugs doxorubicin (Dox) tamoxifen (Tam), 4-hydroxytamoxifen (4-OH-Tam) and endoxifen (End) by carrier proteins, human serum albumin(HSA), bovine serum albumin (BSA) and beta-lactoglobulin (b-LG) were compared in aqueous solution at physiological condition. Doxorubicin, tamoxifen and its metabolites bind serum proteins via hydrophobic, hydrophilic and H-bonding contacts. The loading efficacy (LE) was 45-55% for drug-protein conjugates. Modeling showed the presence of H-bonding, which stabilized drug-protein complexation with the free binding energy of -11.79 to -10.75 for drug-HSA, -13.79 to -9.30 for drug-BSA and -8.12 Kcal/mol for drug-b-LG adducts. Drug conjugation induced major perturbations of the protein conformation. The results indicated that serum proteins are capable of transporting anticancer drugs to target molecules.

Ключевые слова: Doxorubicin, Drug delivery, modeling, tamoxifen, serum protein, loading efficacy