The Construction Of Novel Acid-responsive Hydrogen-releasing Nanomedicine And Its Application In The Treatment Of Tumors And Diabetes

Hydrogen therapy as a kind of gas therapy,compared with carbon monoxide,nitric oxide,hydrogen sulfide and so on,has attracted more and more attention and research due to its unique safety.It is generally believed that hydrogen is a new bioactive substance,which can selectively remove highly toxic reactive oxygen species.Overexpression of reactive oxygen species is one of the characteristics of tumors,so hydrogen is a potential means of cancer treatment.Traditional methods of hydrogen administration,such as oral hydrogen water and hydrogen absorption,have been proved to be effective not only for animal disease models,but also for human diseases.However,because hydrogen is a small molecule gas which is easy to diffuse and has low solubility,it is difficult to achieve long-term and controllable release of hydrogen drugs in tumor sites by traditional drug delivery methods,which greatly affects the further application of hydrogen and the development of hydrogen medicine.The combination of gas therapy and nanomedicine will undoubtedly provide a possibility for the long-term controlled release of hydrogen in the lesion.Nano-hydrogen-releasing medicine can not only realize the loading and delivery of gas prodrugs,but also facilitate the accumulation of gasmedicine in the tumor site by the passive targeting.We chose ammonia borane(AB)as the precursor of hydrogen release,and mesoporous silica nanoparticles(MSN)with high specific surface area and good biocompatibility as carriers to construct an intelligent nanomedicine AB@MSN for acid-responsive hydrogen release by efficiently loading hydrogen predrug inside the carrier.This nano-hydrogen-releasing medicine has good tumor enrichment performance and high hydrogen release,which can responses to the long-term release of hydrogen in the slightly acidic environment of the tumor site.Through the analysis result,it was found a good biological safety and inhibition effect of tumorous volume.On this basis,an oral sustained-release hydrogen nanotablet AB@hMSN@PEG was prepared for the treatment of obesity and diabetes.The oral sustained-release hydrogen nanotablets can release hydrogen responsively under gastric acid conditions.Due to the presence of PEG,the effect of slowly releasing hydrogen can be achieved.Two models of obesity diabetic mice induced by high fat and type 2 diabetic mice were established.The results showed that the oral sustained-release hydrogen nanotablets AB@hMSN@PEG had certain inhibitory effects on obesity and diabetes.The controllable hydrogen-releasing nanodrugs,which are stimulated by endogenous acid environment,provide a new strategy and solution for precise and efficient disease treatment.