A novel multifunctional poly(amidoamine) dendrimeric delivery system with superior encapsulation capacity for targeted delivery of the chemotherapy drug 10-hydroxycamptothecin

With the aim of developing an efficient targeted delivery system for cancer therapy that overcomes drug leakage during circulation, we prepared a novel multifunctional dendrimeric carrier by integrating long hydrophobic C12 alkyl chains, poly(ethylene glycol) chains and c(RGDfK) ligands presented on the surface. This dendrimer was able to tightly encapsulate the hydrophobic anticancer drug 10-hydroxycamptothecin (10-HCPT) through simple complexation and selectively target the drug to cancer cells overexpressing integrin alpha(v)beta(3) through high affinity interactions. The complex has a high loading efficiency, with each molecule encapsulating approximately 20 drug molecules; high stability, without any detectable drug release during dialysis for three days; and high water solubility, achieving an approximately 600-fold increase over the water solubility of free 10-HCPT. This complex exhibited notably high cytotoxicity against 22RV1 cells overexpressing integrin alpha(v)beta(3) and a far lower cytotoxicity against MCF-7 cells, which express low levels of integrin alpha(v)beta(3). We expected encapsulated 10-HCPT to regain its anti-cancer activity following selective internalization of the complex into carcinoma cells via integrin receptor mediated endocytosis. As the drug remains inactive before internalization, this carrier has the ability to overcome problems associated with drug leakage in the circulation and off-target effects on normal tissues. (C) 2014 Published by Elsevier B.V.