Hollow Gold Nanoshells for Near Infra Red Cell by Cell Treatment

Abstract

The temporal and spatial control over the delivery of materials such as siRNA or small molecular weight drugs into specific cells remains a significant technical challenge. We demonstrate the pulsed near-infrared (NIR) laser dependent release of siRNA or the chemotherapy drugs cisplatin and doxorubicin via the thermo-mechanical influence of 40 nm hollow gold nanoshells (HGN). Ligand-receptor interactions promote the cellular uptake of HGNs in targeted cells, resulting in HGN clusters within endosomes in the targeted cells. Non-targeted cells take up individual HGNs or no HGNs. The spatiotemporal silencing of a reporter gene (green fluorescence protein) was studied using photomasking to selectively irradiate targeted cells with NIR light to release chemically bound siRNA and rupture endosomes. GFP silencing followed siRNA release to the cytoplasm in NIR irradiated cells. The NIR laser induced release of siRNA from the nanoshells is found to be power and time dependent, through surface-linker bond cleavage, while the escape of the siRNA from endosomes occurs above a critical pulse energy attributed to local heating and nanobubble formation and collapse (cavitation). The same HGN could be used to selectively increase the permeability of multi-drug resistant cancer cells to doxorubicin or cisplatin to enhance the efficacy and selectivity of conventional chemotherapy. NIR induced nanobubbles enhanced the chemotherapeutic efficacy of liposome encapsulated doxorubicin (Doxil™) 33 times, allowing a reduction in drug dose by an order of magnitude while reducing non-specific toxicity to 15% (from 100%) among normal cells in a model of drug resistant oral cavity squamous cell carcinoma.