In-situ Hydrogen Nanogenerator And Controllable Reactive Oxygen Species Nano-devices For Synergistic Photothermal/Hydrogen Therapies

In chapter 1,The application prospect of hydrogen in the diagnosis and treatment of tumor was briefly described.The methods and research progress of cancer diagnosis and treatment based on nanodrugs were introduced.In chapter 2,Multifunctional nano agents integrating multiple therapeutic and imaging functions hold promise in the field of noninvasive and precise tumor therapies.However,the complex preparation process and uncertain drug metabolism of nano agents loaded with various therapeutic agents or imaging agents greatly hinder its clinical application.Developing simple and effective nanoagents that integrate multiple therapeutic and imaging functions remain a huge challenge.Therefore,a novel strategy based on in-situ hydrogen release is proposed in this work:aminoborane（AB）was loaded onto mesoporous poly dopamine nanoparticles（MPDA NPs）as a prodrug for hydrogen production,and then,PEG was modified on the surface of nanoparticles（represented as AB@MPDA-PEG）.H₂ gas generated by AB in the weak acid condition of tumor microenvironment（TME）not only was used to treat tumors via combination of hydrogen and photothermal therapies,but also serves as US and CT contrast agent,providing accurate guidance for tumor treatment.In vivo and in vitro investigation suggest that the designed multifunctional nano system not only showed excellent properties such as high hydrogen loading capacity,long-lasting sustained hydrogen release ability and excellent biocompatibility,but also achieve selective PTT/hydrogen therapies and US/CT bimodal imaging functions,which can effectively guide antitumor therapies.The proposed hydrogen gas-based strategy for combination therapies and bimodal imaging integration hold promises an efficient and safe tumor treatment for future clinical translation.In chapter 3,since the sensitivity of cancer cells to reactive oxygen species is different from that of normal cells,the strategy of targeting redox system is feasible.Here,we synthesized a kind of nanoparticles that can change their redox properties in response to near-infrared wavelength（PIH@R）.PIH@R It can be used as an exogenous redox regulator and release/eliminate reactive oxygen species in the way we want.Interestingly,PIH@R It can act like a"Trojan horse"in cancer cells:first,under the irradiation of a low-power laser with a wavelength of 1064 nm,PIH@R Camouflaged as reducing species in cells,cancer cells reduce their own reducing substances through redox balance system regulation.Then,after the redox balance in the cells reached a stable state,PIH@R The reactive oxygen species can be continuously released by switching the wavelength of infrared light,so that they can be"subverted"to be oxidizing.because PIH@R The"camouflage"effect of the cell reduces the content of reducing species.PIH@R The change of chemical properties can easily destroy the redox balance and induce apoptosis of cancer cells.The experimental results show that the strategy based on precise regulation of reactive oxygen species can expand the selectivity of photodynamic therapy in cancer cells and normal cells.It is important that,PIH@R It can also be used as a convenient on-demand release device for ROS related disease research,which has great application potential.