Development Of Multifunctional Nanoparticles And Their Application In Combined Hydrogen And Photothermal Therapy For Liver Cancer

Cancer with high incidence rate and mortality has been widely concerned.Among many cancers in China,liver cancer has the fifth incidence rate and the second mortality.To treat liver cancer,scientists develop various treatment methods,such as surgery,chemotherapy,radiotherapy,immunotherapy,photodynamic therapy（PDT）,etc.However,each method has its inherent shortcomings,so a new therapeutic method-gas therapy was developed.For gas therapy,hydrogen（H₂）is widely used because of its minimum molecular weight,high biological safety and strong biological reduction.However,the effect of hydrogen therapy alone is not significant.In order to have a better tumor treatment effect,a combination of multiple treatment methods is usually used.Noninvasive photothermal therapy（PTT）has been widely used because of its advantages such as precision and controllability,strong penetrability,strong specificity,and small side effects.However,the low temperature is easy to make the tumor recurrence,while high temperature is easy to damage normal tissues and cause inflammation.Therefore,we use the combination of hydrogen therapy and photothermal therapy to treat tumors for better therapeutic effect while protecting normal tissues from damage.In this paper,elemental iron embedded in mesoporous carbon nanoparticles（C/Fe NPs）with hydrogen-producing and photothermal properties were synthesized by a simple and repeatable method.Due to the weak acidic microenvironment of the tumor microenvironment,the C/Fe NPs will release hydrogen.The released hydrogen react with the highly toxic·OH at the tumor site,which will unbalance the oxidation-reduction homeostasis at the tumor site and cause oxidative stress,so as to achieve the therapeutic effect of hydrogen.At the same time,the carbon in C/Fe NPs with strong photothermal conversion efficiency can convert light energy into heat energy under laser irradiation,when it gathers at the tumor site,which will increase the temperature of the tumor site to achieve the purpose of photothermal treatment.The in vitro/vivo experiment also further proved that the synergistic effect of H₂/PTT can inhibit tumor to the maximum extent,and has little effect on normal cells.In order to explore the effect of H₂/PTT therapy on tumor of nanoparticles loaded with hydrogen prodrug,we synthesized dopamine nanoparticles coated with polyacrylic acid-aminoborane nanoparticles（PAA-AB@PDA NPs）in a simple way.Here,AB is an efficient hydrogen storage prodrug with sensitive acid reactivity.It can release hydrogen through controlled acid reaction at the tumor site to achieve the purpose of hydrogen therapy.At the same time,the PDA in the nanoparticles has good photothermal conversion efficiency,which can increase the temperature of the tumor site under laser irradiation to achieve the purpose of photothermal treatment.Through comparative experiments in vitro/vivo,it can be clearly found that the synergistic anti-tumor effect of PAA-AB@PDA NPs is significantly stronger than that of hydrogen therapy alone or photothermal therapy alone.Therefore,H₂/PTT synergetic therapy is a better choice for anti-tumor,which provides new ideas for researchers.