Nanoprobes Based On Photoacoustic Imaging In The Second Near-infrared Window For Chemotherapy Combined With Chemodynamic Therapy Of Colon Cancer

Malignant tumors are deadly disease that seriously threatens human health and life.Colon cancer has become the third highest cause of death in worldwide.For most cancer patients,precise diagnosis and treatment are necessary to improve survival rates and cure cancer.Various therapeutic methods have been developed to combat them,including surgery,radiotherapy and chemotherapy.However,the development of these traditional treatment strategies was hindered because of serious side effects and limited efficacy.Therefore,potential and emerging technologies for cancer treatment,such as chemodynamic therapy（CDT）,immunotherapy,and targeted therapy,have been developed.In addition,combining multiple treatments can provide a more effective strategy for tumor treatment.Chemotherapy drugs can effectively kill cells through various mechanisms.However,conventional chemotherapeutic drugs suffer from the limitations of serious side effects,low bioavailability and nonspecific distribution.Moreover,multidrug resistance as a primary challenge in tumor therapy always causes the failure of chemotherapy or increases effective dosage of chemotherapy drugs.Tumor microenvironment responsive-nanomedicine can effectively overcome the above difficulties.However,the distribution of nanomedicines and the release of chemotherapy drugs are crucial for cancer treatment.Therefore,it is necessary to construct multifunctional nanomedicines with imaging and therapeutic effects.In this study,the PVP-modified 2D nanosheet-like metal-organic framework materials（MOFs）were obtained through a one-step hydrothermal method with Cu²⁺as metal ions and ellagic acid（EA）as bridging ligands.The nanoprobe（Cu/EA-MOF）exhibit excellent stability under physiological conditions and good biocompatibility.Firstly,the nanoparticles accumulate at the tumor site through the enhanced permeability and retention（EPR）effect.Then,the nanoparticles response to hydrogen sulfide（H₂S）The nanomedicine responding with the high expression of hydrogen sulfide（H₂S）in colon cancer releases the chemotherapeutic EA and generates copper sulfide nanoparticles(Cu_2-xS).The copper ions can react with the high level of hydrogen peroxide（H₂O₂）through a Fenton-like reaction and generate a large amount of hydroxyl radicals,which disrupt the redox balance of the tumor microenvironment and kill tumor cells.EA,as a natural polyphenol,can effectively inhibit tumor growth.Meanwhile,EA can also cause the increase of superoxide dismutase（SOD）level and the decrease of catalase（CAT）level,which can enhance the therapeutic efficacy of CDT by increasing the H₂O₂ level in tumor.Therefore,Cu/EA-MOFs can achieve combined chemotherapy and chemodynamic therapy.Moreover,the absorption spectra of Cu/EA-MOF mainly locate in the second near infrared window（NIR-Ⅱ）with the peak at 1280 nm,which was beneficial for deep tissue penetration due to the reduced light scattering and absorption in biological tissues.With increasing H₂S concentrations,the photoacoustic（PA）signal intensity increase dramatically at 950 nm and decrease at 1280 nm,resulting in the detection of H₂S and the monitoring of drug release by the ratiometric NIR-Ⅱ PA imaging.The variations in NIR-Ⅱ PA ratios provided precise and quantitative drug release,correlated with the therapeutic effect.In this study,we have prepared a theranostics nanoprobe by a simple chemical coordination process.The nanoprobe exhibited high sensitivity,excellent selectivity,and stability.It can achieve precise and effective treatment of colon cancer by H₂S-responsive drug release and ratiometric NIR-Ⅱ PA imaging.The nanoprobe is expected to provide important reference value for the treatment and efficacy prediction of clinical malignant tumors.