No-Release Nanoplatforms Based On Organic Framework Materials For Synergistic Cancer Therapy

Cancer is a disease caused by the loss of normal regulation of the body’s cells and excessive proliferation,also known as malignancy.These over-proliferated cells may compress,squeeze,and destroy surrounding tissues or organs,causing organ failure.Currently,the main clinical treatments for cancer include surgery,chemotherapy,and radiotherapy.Surgery can maximize the removal of visible tumor tissue,but it is more invasive and carries surgical risks.Chemotherapy refers to the direct killing of cancer cells by chemical drugs,but chemotherapeutic drugs need to be administered systemically and can also have toxic side effects on normal cells.Radiotherapy is a local treatment method using radiation to treat tumors.The efficacy of radiotherapy depends on the sensitivity of radiotherapy,and the treatment effect is poor for tumors with low sensitivity to radiotherapy.In recent years,a number of new cancer treatment methods have emerged,including photodynamic therapy,photothermal therapy,chemodynamic therapy,and so on.Gas therapy induces cancer cell death using several gas transmitters such as carbonic oxide,hydrogen sulfide,hydrogen,nitric oxide（NO）,and sulfur dioxide.The key to gas therapy is the accumulation of sufficient gas in the tumor tissue.However,most gas prodrugs have difficulty in achieving active accumulation in the tumor and the ability to control gas release.Therefore,it is necessary to develop gas prodrugs delivery nanoplatforms to achieve responsive gas release.Combining gas therapy with photodynamic therapy or chemodynamic therapy is expected to improve the effectiveness of cancer treatment.For example,when NO therapy is combined with photodynamic therapy,NO gas can cause vasodilation in the vicinity of the tumor,enhancing blood circulation in the tumor area and thereby enhancing the efficacy of photodynamic therapy by increasing the oxygen supply.Based on this,two organic framework materials have been designed and prepared for the delivery of NO donors in combination with other therapeutic modalities for cancer treatment.1.In this part,a porphyrin-containing covalent organic framework（COF）was developed as a glutathione（GSH）-responsive NO donor benzofuroxan delivery nanoplatforms for synergistic cancer therapy.When the nanoplatforms reach the tumor tissue,a high concentration of GSH reacts with benzofuroxan to produce NO,and a high concentration of NO can directly cause cell death.After laser irradiation,COF acts as a photosensitizer to produce highly cytotoxic ROS for photodynamic therapy of tumors.More importantly,the production of NO is accompanied by the consumption of GSH,and the reduction of GSH levels can effectively reduce the consumption of ROS produced by the photosensitizer,thus improving the efficiency of photodynamic therapy and achieving a"1+1>2"synergistic cancer treatment.2.In this part,an iron-containing metal-organic framework（MOF）nanoplatforms was designed and prepared for the delivery of NO prodrug（L-arginine）and oxaliplatin.When the nanoplatforms reach the tumor tissue,GSH reduces Fe³⁺in the MOF to Fe²⁺triggering the collapse of the skeleton and releasing the prodrugs L-arginine and oxaliplatin.Fe²⁺then catalyzed overexpressed hydrogen peroxide in tumor cells to generate hydroxyl radical（·OH）,which induced cell apoptosis.In addition,·OH also activates the release of NO from L-arginine,reversing the drug resistance of tumor cells,sensitizing resistant cells to oxaliplatin,and improving the efficiency of chemotherapy,enabling efficient treatment of drug-resistant colon cancer.