We have developed a new drug delivery system for increasing the efficacy of anticancer drugs by employing the biocompatible, non-immunogenic, and non-toxic, water-soluble N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer conjugates equipped with oligopeptides as targeting ligand that can bind selectively to tumor vascular endothelial cells. These conjugates contained the anticancer drug Doxorubicin (DOX) and a specific peptide sequence (named 'Esbp', primary sequence DITWDQLWDLMK) that can selectively bind with high affinity to E- selectin, which is a molecular marker expressed exclusively by vascular endothelial cells during inflammation and cancer.
In vitro cytotoxicity of DOX- HPMA-peptide copolymers against TNFa activated (solid lines) and non-activated (dashed lines) IVECs, as determined by MTT assay. (®, red) free DOX drug; (¡, blue) P-(Esbp)-DOX; (Δ, black) P-(Scrm)-DOX; and (, green) P-DOX. P-(Esbp)-DOX presented higher cytotoxicity against TNFa activated cells while all other controls, including using P-(Scrm)-DOX with scrambled peptide sequence, did not. The IC50 for P-(Esbp)-DOX in these assays was found to be 0.3 mM
Targeted anti cancer drug delivery (e.g Doxorubicin)