Preparation Of Endogenous NO-release Carbon Nanodots For Cancer Therapy

At present,the treatment of cancer is mainly about surgical resection,chemotherapy and radiotherapy.They all have some side effects.Gas therapy is an emerging treatment method,which has become one of the hotspots in anti-tumor research due to its little side effects in recent years.In this paper,carbon nanodots are selected as nitric oxide?NO?donors for the first time,and they are applied in anti-cancer therapy.The main contents are as follows:?1?In this work,we prepared some kinds of carbon nanodots using L-arginine as reagent through microwave.The NO release profiles indicate that the carbon nanodots can release more NO when the molar ratio of L-arginine to ethanediamine is2:1,which are labeled as the Arg-dots.The Arg-dots generally exhibit spherical shape with average diameters mainly about 3 nm,and there are lots of guanidyl groups on the surface.Besides,through the exploration of the excellent fluorescence properties,the as-prepared Arg-dots emit strong blue fluorescence under ultraviolet light in solution.The NO release profiles showed the Arg-dots possess the long half-life period and retention time in the blood.With an increase of H₂O₂ concentration,both NO release amount and release rate of the Arg-dots were increased markedly.Compared with the influence of H₂O₂,the effect of pH is very limited to the NO release of the Arg-dots.?2?In order to investigate the intracellular localization of the Arg-dots,A549tumor cells were treated with the Arg-dots together with 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate?DAF-FM DA?,a commercial NO-sensitive fluorescent probe.The intracellular localization of the Arg-dots and DAF-FM DA can then be visualized by using inverted fluorescent microscopy under different FL channels,indicating that the Arg-dots can enter tumor cells by uptake and release NO,and can be applied as a fluorescent probe in cell imaging.In order to evaluate the anti-tumor activity of the Arg-dots,four kinds of tumor cells as well as one kind of normal noncancer cell,were chosen to incubate with various concentrations of the Arg-dots.The results demonstrated that the Arg-dots are ideal anti-tumor reagents,safe for the normal cells but toxic for the cancer cells.To gain more insight into the treatment effect of the Arg-dots against multi-drug resistant?MDR?,multidrug resistant cell line MCF-7/ADR was chosen to incubate with the Arg-dots and DOX.The Arg-dots can also reverse MDR phenomenon,and increase the therapeutic effect of anti-cancer drugs in MDR cell lines.The H&E stain of tumor tissues in different groups did not show serious damage in all groups.The body weights did not decrease after treatment with the Arg-dots.It suggested that the Arg-dots have good biological compatibility,which provides a potentially multifunctional nanoplatform for further applications in cancer therapy.