Study On The Performance Of Defect-rich LDHS Materials In Tumour Sonodynamic Therapy

Cancer has become the number one killer threatening human health in this century.With the deepening of industrialization,the incidence rate of cancer has increased year by year due to the influence of air pollution,environmental damage,accelerated pace of life,smoking and drinking habits and other factors.At present,the traditional cancer treatment methods include surgery,radiotherapy,chemotherapy,etc.There are still some shortcomings,such as greater trauma,difficult surgery in some parts,inability to completely eliminate cancer cells,large side effects and strong drug resistance,which seriously affect the effect of cancer treatment.Sonodynamic therapy（SDT）,a new non-invasive and accurate tumor therapy,has emerged in recent years.SDT makes use of the characteristics of sonosensitizers gathering in tumor cells,and uses special ultrasound to activate sonosensitizers after precise imaging positioning under non-invasive conditions,so as to generate singlet oxygen species（ROS）through chemical reaction,and achieve the goal of accurate and complete killing of tumors.Because sound waves penetrate deeper into tissues,SDT is applicable to large tumors that are difficult to be treated by photodynamic therapy or tumors embedded in the internal organs.It is a promising non-invasive tumor treatment method and has great advantages compared with conventional photodynamic therapy.There are mainly two kinds of sonosensitizers widely reported.One is organic sonosensitizers,such as various porphyrin derivatives,and the other is inorganic sonosensitizers,among which Ti O₂nanoparticles are the most common.However,the stability of organic sonosensitizers under ultrasound is often limited,and most organic sonosensitizers are also photosensitizers.Therefore,their phototoxicity and skin sensitivity still have some problems after cancer treatment.Compared with organic sonosensitizers,inorganic sonosensitizers such as Ti O₂nanoparticles have higher chemical stability and lower phototoxicity,and are expected to be used in highly effective SDT treatment.In inorganic nanoparticles,the rapid combination of electrons（e^-）and holes（h⁺）（50±30 ns）leads to a low quantum yield of ROS,which limits their efficiency in SDT.Therefore,the development of highly sonosensitizers with imaging function plays a crucial role in improving the performance of SDT.So far,layered double hydroxides（LDHs）and their nanocomposites have been widely used in various cancer treatments,including traditional chemotherapy,emerging phototherapy,gene therapy,etc.LDHs can develop more effective antitumor therapy by virtue of their adjustable two-dimensional layered nanostructures,good biocompatibility and controllable chemical composition.In addition,defect strategy has also been proven to significantly improve the ROS generation capacity of nanomaterials,but the structure-activity relationship between the generation of defects and the SDT performance of LDHs remains to be studied.Therefore,based on the above ideas,we designed and synthesized CoMnMo-LDH nanosheets,and induced a large number of defects through acid etching,making them become highly active sonosensitizers with imaging function.The research contents and results of this paper are as follows:1.Preparation of defect-rich LDHs nanosheets and study on their SDT properties2D CoMnMo-LDH nanosheets were synthesized by co-precipitation method in an oil pan at 80℃,and defect rich CoMnMo-LDH（DR-CoMnMo-LDH）nanosheets were obtained by simple acid treatment.The research shows that DR-CoMnMo-LDH nanosheets have good ROS generation ability under US irradiation,and its ¹O₂generation activity is 9times that of Ti O₂nanoparticles.The efficient SDT performance of 2D DR-CoMnMo-LDH can be attributed to the narrowing of the band gap caused by a large number of defects produced by acid etching,thus improving the separation efficiency of electron-hole pairs.2.The defect-rich LDHs nanoplatform is used for magnetic resonance imaging（MRI）and in vivo and in vitro treatmentAfter the above DR-CoMnMo-LDH were modified with polyethylene glycol 2000（PEG-2000）,the in vitro cell experiment was carried out.First,the biocompatibility of DR-CoMnMo-LDH-PEG to 4T1 cells was evaluated by MTT method.Subsequent studies found that DR-CoMnMo-LDH-PEG can generate a large amount of ROS under US irradiation,and generate O₂to promote SDT performance in the presence of tumor endogenous hydrogen peroxide（H₂O₂）.Secondly,4T1 tumor-bearing mice were selected for DR-CoMnMo-LDH-PEG anti-tumor study in vivo,and 4T1 tumor-bearing mice were imaged with MRI in vivo.The above results show that this defective LDHs nanoplatform can effectively accumulate at the tumor site,and produce a large amount of ROS under US irradiation,so as to achieve good anti-tumor effect.Finally,the histological examination of the main organs of mice,hemolysis experiment and metabolism experiment were carried out,and the results showed that the material has good biological safety.Therefore,DR-CoMnMo-LDH-PEG can be used for efficient SDT cancer treatment.In conclusion,in this paper,we have obtained defect-rich LDHs nanosheets with MR imaging and therapeutic functions by acid treatment strategy.It is found that this defect-rich CoMnMo-LDH nanosheets have the ability to efficiently produce ROS and good biosafety,so it can become a potential effective sonosensitizer.