Construction Of Defect-rich LDHs Materials And Their Photodynamic Therapy Properties

Among many diseases,the incidence of cancer has always been high.Traditional cancer treatment methods（surgery,chemotherapy and radiotherapy）still have the deficiencies of high recurrence,large side effects and strong drug resistance,which seriously affect the effect of cancer treatment.Photodynamic therapy（PDT）is a novel cancer treatment with low trauma,low side effects and high selectivity.At the heart of PDT are photosensitizers（PSs）,which absorb light to produce reactive oxygen species（ROS）that can induce cancer cells apoptosis.Therefore,the development of highly active PSs plays a crucial role in realizing the great improvement of PDT performance.Inorganic nanomaterials have been widely used in PDT due to their superior properties.Compared with the widely developed organic PSs,inorganic PSs have the characteristics of superior photostability and easy accumulation at tumor sites.Therefore,the design of inorganic PSs with high ROS generation capacity and long wavelength excitation has been the focus of researchersIn recent years,two-dimensional（2D）layered double hydroxides（LDHs）,as typical inorganic nanomaterials,have been widely used in the field of biomedicine due to their good biocompatibility and easily tunable structures.Based on the unique advantages of LDHs monolayer structure and confinement effect,combined with the principle of PDT treatment,a large number of LDHs composite photosensitizer materials have been constructed,which proves its excellent cancer treatment effect.In addition,the defect-based strategy has also been shown to be an effective strategy to significantly enhance the photocatalytic and electrocatalytic activities of LDHs nanomaterials,but the effect of defects on the PDT performance of LDHs remains to be studied.Therefore,based on the above research ideas,we designed and synthesized ultrathin CoMo-LDH and NiMo-LDH nanosheets,and activated them by acid treatment to induce a large number of defects,making them as highly active PSs for near-infrared III（NIR-III）PDT.The research contents and related results of this paper are as follows:1.Preparation of defect-rich Mo-based LDH nanosheets and investigation of their NIR-III PDT performanceUltrathin 2D CoMo-LDH and NiMo-LDH nanosheets were synthesized by co-precipitation and then etched via a simple acid treatment to obtain defect-rich CoMo-LDH（DR-CoMo-LDH）and NiMo-LDH（DR-NiMo-LDH）nanosheets.The results showed that the DR-CoMo-LDH nanosheets exhibited good ROS generation activity under NIR-III 1567 nm laser irradiation,and its¹O₂ generation activity was 97 times higher than CoMo-LDH nanosheets.The efficient PDT performance of 2D DR-CoMo-LDH can be attributed to band gap narrowing caused by defects produced by acid etching,allowing it to be excited by low energy light.Under 1567 nm laser irradiation,the photogenerated electrons and holes generated in the DR-CoMo-LDH nanosheets occupy the conduction band（CB）and valence band（VB）,respectively.The photoelectrons are ejected into the surrounding environment and react with O₂ to form the intermediate·O₂^-,which can further combine with holes to form the final ¹O₂.2.In vivo and in vitro antitumor effects of defect-rich Mo-based LDH nanosheetsIn vitro cell experiments were performed after surface modification of defect-rich LDH with PEG.Firstly,the good biocompatibility of DR-CoMo-LDH-PEG in 4T1,MREpi C and Cos-7 cells was verified by MTT assay.Then we evaluated the PDT performance of DR-CoMo-LDH-PEG on4T1 cells and found that DR-CoMo-LDH-PEG could be excited by 1567 nm light to generate a large amount of ROS.Moreover,the presence of tumor endogenous hydrogen peroxide（H₂O₂）can generate O₂,which further promotes PDT performance.Finally,4T1 tumor-bearing mice were selected to investigate the in vivo PDT anticancer activity of DR-CoMo-LDH-PEG.The study showed that defect-rich LDHs nanosheets can be significantly enriched at tumor sites,and the generation of large amounts of ROS under 1567 nm light irradiation can achieve significant tumor ablation.In addition,both the histological examination of the main organs of the mice injected with DR-CoMo-LDH-PEG and PBS,and the red blood cell hemolysis experiment showed that DR-CoMo-LDH-PEG has good biological safety.Therefore,DR-CoMo-LDH-PEG is promising to be used as a highly active PSfor efficient PDT.In conclusion,defect-rich LDHs nanomaterials obtained by acid-etching can be used as highly active PSs for photodynamic cancer therapy in the NIR-III window.We found that such a defect engineering strategy can significantly enhance the ROS-generating activity of CoMo-LDH nanosheets,making them effective PSs for cancer cell depletion in vitro and tumor ablation in vivo under NIR-III 1567 nm laser irradiation.