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

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