اکسید گرافن احیا شده فرا کوچک با جذب بالای فروسرخ نزدیک برای نور گرما درمانی

ABSTRACT Ultrasmall Reduced Graphene Oxide with High Near-Infrared Absorbance for Photothermal Therapy

Photothermal therapy employs photosensitizing agents taken up by cells to generate heat from light absorption,1 leading to photoablation of the cancer cells and subsequent cell death. To avoid nonspecific heating of healthy cells, photosensitizers must show high absorption in the near-infrared (NIR)1 and selective uptake in cancerous cells in tumors over normal cells in healthy tissues. Deep penetration and little nonspecific photothermal heating in the NIR window are due to the transparency and low absorption of light by tissues in this optical window.2 Materials currently under investigation with high optical absorbance in the NIR region for photothermal therapy include gold nanoshells,3 gold nanorods,4-6 gold pyramids,7 single-walled carbon nanotubes (SWNTs),8-10 and multiwalled carbon nanotubes.11 Graphene Oxide (GO) has recently emerged as a novel material in nanocarbon research.12,13 An abundant and low cost material synthesized from graphite, GO has potential use in energy,14,15 electronics,16 molecular sensing areas,17 and catalysis.18 A new direction for GO is in the field of biomedicine.

Previous studies on non reduced, covalently PEGylated graphene oxide (nano-GO) demonstrated effective in vitro drug delivery 19 and in vivo photothermal heating 20 using relatively high injected doses (∼20 mg/kg) and NIR laser powers (∼2 W/cm2) as compared to carbon nanotubes.8-10 The high dose/power needed for photoablation was due to the suboptimal absorption of NIR light by nano-GO in a highly oxidized form.

Here, we developed nanosized, reduced graphene oxide (nano-rGO) sheets with noncovalent PEGylation. The nanorGO was derived by chemically reducing covalently PEGylated nano-GO to partially restore the aromatic, conjugated character of graphene sheets, affording an increase in NIR absorbance by >6-fold. Because of the lack of functional groups on reduced GO, a branched amphiphilic surfactant was used to coat nano-rGO noncovalently for stability and biocompatibility in biological buffer solutions. The resulting nano-rGO allowed for peptide conjugation for cancer cell targeting and selective photoablation of cancer cells at a low dose. This is the first time GO in reduced form with noncovalent PEGylation is developed for biological applications, establishing nano-rGO as a highly effective photothermal agent with comparable absorbance of NIR light to gold and carbon nanotube materials.