Antibacterial And Anti-tumor Effects Of Hydrogel With Laser-controlled NO Release And Sustained Berberine Release Function

At present,both bacteria and cancer are serious diseases that threaten human health.Berberine,a natural compound,is a commonly used antibacterial agent,which plays an important role in treating gastroenteritis and bacillary dysentery.In recent years,a large number of experimental results show that berberine can be used for tumor treatment,and berberine has obvious therapeutic effects on gastric cancer,breast cancer and liver cancer.However,kinds of problems such as poor water-solubility,poor targeting and low bioavailability of natural compounds have hindered their efficacy seriously.It can be seen that finding ways to improve the bioavailability of berberine with low-toxicity will effectively improve the utilization value.Nitric oxide（NO）is a gas endogenous messenger that is almost ubiquitous in mammalian cells.Recent studies have shown that high concentrations of NO have good antibacterial and good anti-tumor effects.NO mainly relies on active nitrogen oxides（RNOS）produced by the interaction with reactive oxygen species（ROS）to exert antibacterial and anti-tumor effects.However,NO has disadvantages such as the extremely short half life,limited water solubility and high chemical reactivity to oxygen,superoxide,metalloenzymes,and mercaptans,make it difficult to target to the lesion site and accumulate a large amount of NO to the target location.Using NO donors to construct a controlled release system is an effective method to increase the concentration of NO at the target location.Rare earth doped upconversion nanomaterials（UCNP）can absorb low energy light（near infrared light）and convert it into high energy light（visible or ultraviolet light）,which can break chemical bonds.Mesoporous silicon dioxide（Si O₂）has advantages such as high specific surface area,adjustable pore size,and excellent biocompatibility.In recent years,Si O₂has gradually become an efficient carrier.Based on the above background,this paper uses up conversion nanomaterials with surface modified Si O₂to load NO donor,and establish a NO controlled release system.The system was co-loaded with berberine in a thermosensitive hydrogel to achieve NO controlled release and berberine sustained release,and achieve the joint action of NO and berberine in anti-tumor and antibacterial treatment.The sample morphology characterization results show that UCM exhibits an elliptical spherical shape with pores,the average particle size is about 90 nm;The results of nitrogen adsorption and desorption experiments show that the total pore volume of the sample is 642.95 m²·g^-1,and the average pore diameter is 12.8 nm;The X-ray energy spectrum analysis results show that the sample is mainly composed of five elements:Y,Yb,Tm,O,and F.The NO release performance test experiment shows that the controlled release of NO can be achieved using near-infrared laser,and the release of NO has concentration dependence and time accumulation;The results of drug release experiment showed that hydrogel had the ability of self swelling and degradation in water,and could release drug slowly and completely.Finally,the results of anti-tumor experiments in vitro showed that the survival rate of 4T1 cells co incubated with UCMS+BBR-gel was less than 20%,which indicated that the anti-tumor performance of BBR was improved to some extent by co-incubating with NO.In vitro and in vivo antibacterial experiments showed that the inhibition rates against Staphylococcus aureus and Escherichia coli reached 97%and 80%,reducing bacterial survival;After the antibacterial effect of the material,the hydrogel further protects and repairs the wound coverage,and accelerates the wound healing.In conclusion,this paper established a multifunctional hydrogel system consist of berberine and up conversion materials based NO controlled release system,which can realize sustained drug release and controlled nitric oxide release for anti-tumor and antibacterial treatment.The synthesized UCM is used to load the NO donor SNO,and the obtained nanoparticles with NO controlled release function and natural drug BBR are wrapped in the thermal sensitive hydrogel system prepared by Pluronic F127/F68.Under 980 nm near-infrared light irradiation of UCNP,low-energy infrared light converted into high-energy blue violet light,leading to the breaking of S-NO bond to release NO,and the thermosensitive hydrogel slowly releases BBR.After 980nm near-infrared radiation,the hydrogel treatment group could achieve 80%inhibition of 4T1 cancer cell activity;It can inhibit the activity of about 97%of S.aureus and nearly 80%of E.coli,and accelerate wound healing.