Nano-oxide Combined With Metal-Organic Framework For Photodynamic Therapy Of Tumors

Cancer has become one of the major diseases that seriously threaten human health.Traditional treatments for cancer are mainly surgical treatment,chemotherapy,and radiotherapy.Surgical treatment is risky,invasive,and does not suppress metastatic lesions.Chemotherapeutic drugs are non-specific treatments that are more damaging to normal cells.Radiotherapy is not applied for metastatic tumors.Photodynamic therapy has been widely studied in cancer therapy due to its advantages of minimally invasive,high specificity,and low side effects.However,anoxic microenvironment and poor targeting of photosensitizers limit its therapeutic efficiency.In this paper,two in situ oxygen generation systems were constructed by combing hyaluronic acid（HA）modified nano oxide with porphyrin organic framework（PCN-224）.The strategy effectively solved the problem of hypoxia in tumor tissue and tumor photodynamic targeted therapy,and significantly enhanced the effect of PDT on tumors.（1）PCN-224 nanoparticles were prepared by using the solvothermal method.Then,HA-modified CeO₂ was synthesized at room temperature.Finally,PCN-224@CeO₂-HA was obtained by the coordination of Zr⁴⁺and carboxylate in HA.CeO₂ can catalyze overexpressed H₂O₂ in tumor cells to produce O₂ to alleviate hypoxia.HA can specifically target CD44 receptors that are highly expressed on tumor cell membranes to achieve targeted therapy.Cell survival rate experiments showed that PCN-224@CeO₂-HA could effectively alleviate hypoxia in tumor tissues and significantly kill 4T1 and MCF-7 cells.Cell imaging experiments showed that PCN-224@CeO₂-HA could effectively enrich in tumor sites.The mouse tumor model was constructed and analyzed in vivo,the results showed that PCN-224@CeO₂-HA can effectively inhibit tumor growth under 650 nm laser irradiation and showed good biological safety.（2）According to the coordination principle,HA-modified Co₃O₄ nanoparticles were decorated on the surface of PCN-224 to construct PCN-224@Co₃O₄-HA.Co₃O₄can catalyze highly expressed H₂O₂ in tumor cells to produce oxygen to alleviate hypoxia problems.Co₃O₄ can also produce hydroxyl radicals by the Fenton-like reaction for chemodynamic therapy,which significantly improves the effect of PDT.Cell viability assay showed that the cell viability of 4T1 and MCF-7 cells only were40%and 43%in the hypoxia condition.This indicated PCN-224@Co₃O₄-HA can relieve hypoxia at the tumor site to enhance the effect of PDT.Cell uptake assays demonstrated that PCN-224@Co₃O₄-HA had effective tumor-targeting activity.Mouse experiments showed that PCN-224@Co₃O₄-HA has good biological safety.PCN-224@Co₃O₄-HA can effectively inhibit tumor growth by enhancing and targeting PDT and CDT.