In Situ Sulfidation Of Copper-based Nanomaterials By Endogenous H₂S For Colon Cancer Diagnosis And Treatment

Hydrogen sulfide?H₂S?,which has been proven to have many important biological functions in human health and disease,plays an important role in the proliferation and metastasis of colon cancer.Owing to the selectively upregulates the H₂S-producing enzyme cystathionine-?-synthase?CBS?of colon cancer,the concentration of H₂S in cancer tissue is much higher than that in the non-cancerous peritumor tissue.Compared with the near-infrared photothermal reagents that have been developed in recent years,using a special tumor microenvironment as a trigger to achieve tumor diagnosis and treatment can reduce signal interference and damage to normal tissues.Therefore,in this paper,the high-expression endogenous H₂S as trigger,we have developed two reagents for the diagnosis of colon cancer.Details as follows:The first part,we prepared a Cu₂O nanomaterial.The nanomaterial reaches to the colon tumor site after intravenous injection,it reacts with the endogenous H₂S in situ at the colon cancer to generate Cu₉S₈.Cu₂O almost no absorption in the near infrared region,is sulfided to Cu₉S₈,which has strong absorption in the near infrared.Thereby triggering the functions of photoacoustic imaging and photothermal therapy.In vitro and in vivo experiments have proved that Cu₂O can react with H₂S to form Cu₉S₈.H₂S activated in situ reaction for colon cancer diagnosis and treatment has excellent photoacoustic imaging and photothermal therapy effects in vitro and in vivo.This work established a simple and effective colon cancer diagnosis and treatment strategy,and provided a new way for colon cancer treatment.The second part,based on the research work in the first part,we prepared Cur@HKUST-1@PVP nanocomposites.Cur@HKUST-1@PVP can react with the over-expressed H₂S in colon cancer to generate copper sulfide.At the same time,the destruction of the metal-organic framework releases the chemotherapeutic drug curcumin,thereby achieving endogenous H₂S-activated chemotherapy/photothermal treatment.We studied the loading of curcumin by HKUST-1,photoacoustic imaging and the effects of chemotherapy/photothermal therapy in vitro and in vivo.In vivo treatment experiments have proven that the tumor growth of mice has been greatly inhibited after treatment,indicating that the material has a good effect of combined chemotherapy/photothermal treatment.