Control of surface ligand density on gold nanoparticles for breast cancer drug delivery

Abstract

The development of nanotechnology has been in a close relationship with the revolution of biomedical fields, especially in the area of cancer therapy. Researchers have previously shown that gold nanoparticles (AuNPs) can be used for therapeutic purposes with limited cytotoxicity. These AuNPs can be surface modified to impart a level of cell specificity. Consequently, in this project we aim to develop a novel bi-functional AuNP. The 15 nm AuNP was first modified with polyethylene glycol (PEG) with Mw = 5 kDa, then with a neuropeptide Y1 (NPY1) as targeting ligand for specific breast cancer cells, and finally with an aptamer AS1411 as a therapeutic agent, acting as an mRNA destabilizer of the anti-apoptotic gene in cancer cell. We have firstly identified that approximately 500 thiolated PEG-NPY1 strands alone are enough to cover the AuNP surface. Furthermore, around 310 strands of thiolated PEG-NPY1 (Mw ~ 6.6 kDa) and 95 strands of thiolated AS1411 (Mw ~ 9.9 kDa) were attached to the surface of citrate-capped AuNP 15 nm. The bi-functionalized AuNPs exhibited fair cytotoxicity towards target cell MCF-7: 0.5 to 5 nM of these AuNPs resulted in 20 to 40% cell viability decrease. The cellular uptake study still needs to be carried out to verify and optimize this bi-functionalized AuNPs to exhibit a safer and more effective breast cancer treatment.

Date of Award	2015
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology