Jornal de Nanomedicina e Nanotecnologia

Abstrato

Tumor Necrosis Factor Related Apoptosis Inducing Ligand-conjugated Near IR Fluorescent Iron Oxide/Human Serum Albumin Core-shell Nanoparticles of Narrow Size Distribution for Cancer Targeting and Therapy

Itay Levy, Igor Grinberg, Benny Perlstein, Enav Corem-Salkmon and Shlomo Marge

Although much progress has been made in the field of cancer therapy, cancer remains one of the leading causes of death in the western world. Here we have designed and studied a unique type of composite multi-functional near IR (NIR) fluorescent iron oxide (IO) nanoparticles (NPs) of narrow size distribution for tumor targeting and therapy. These NPs were prepared by nucleation followed by controlled growth of thin films of IO onto Cy7-conjugated gelatin nuclei and coated with human serum albumin (HSA) by a thermal precipitation process. The hydrodynamic diameter of these core-shell NPs could be easily controlled by altering the precipitation reaction temperature. For targeting and an anti-cancer effect, we conjugated the Tumor Necrosis Factor Related Apoptosis Inducing Ligand (TRAIL) cytokine to the surface of the NIR fluorescent IO/HSA NPs via a polyethylene glycol (3 kDa) linker. The conjugated TRAIL exhibited enhanced and prolonged anti-cancer activity in both human glioblastoma multiforme and colon cancer cell lines. Further, the combination of these IO/HSA-TRAIL NPs with the commonly used chemotherapeutic drug doxorubicin resulted in a synergistic anti-cancer effect on these cancer cell lines. In addition, we also clearly demonstrated by topically and IV administrations the specific targeting effect and the synergistic therapy effect of the NIR fluorescent NPs in-ovo, by using a chicken embryo model of tumors derived from the various human cancer cell lines.