Research On The Metal-organic Framework Combined With Nano-peroxides For Photodynamic Therapy Of Tumors

Malignant tumor has become one of the main diseases leading to human death,seriously threatening human health.Currently,the treatment of tumors mainly includes chemotherapy,radiotherapy,surgery and photodynamic therapy(PDT).Among them,PDT has attracted much attention due to its advantages of high selectivity,less trauma and less side effects.However,hypoxia in tumor microenvironment severely limits the efficacy of PDT.Metal-organic frameworks(MOFs)have shown broad application prospects in the fields of tumor marker detection,drug loading and PDT due to the diverse structure,easy modification of pores and good permanent biocompatibility.In this paper,two self-generated oxygen nanoplatforms were constructed by combining MOFs and nano-peroxides and further modifying the target group.The strategy not only effectively solved the hypoxia problem,but also improved the PDT efficacy through targeted therapy.The specific works are as follows:(1)Hf-MOF was synthesized by solvothermal method using Hf⁴⁺and porphyrin ligand.Magnesium peroxide(Mg O₂)nanoparticles were deposited on the Hf-MOF surface by in situ oxidation method.The aptamer(DNA)of breast cancer cell line 4T1 was modified on Hf-MOF-Mg O₂ by Hf-O coordination to obtain Hf-MOF-Mg O₂/DNA.Mg O₂ can release oxygen in water to solve the hypoxia problem,further improving the efficacy of PDT.DNA can specifically target breast cancer cells to achieve targeted PDT.The experiments of cell survival rate and cell imaging analysis showed that Hf-MOF-Mg O₂/DNA has good biocompatibility,effectively alleviates tumor hypoxia and enhances the efficiency of targeted PDT.In addition,Hf-MOF-Mg O₂/DNA showed significant tumor inhibition through enhanced and targeted PDT in vivo experiments(2)PCN-224 nanoparticles were synthesized firstly.Then,hyaluronate(HA)-modified calcium peroxide(Ca O₂)nanoparticles were decorated on PCN-224 in situ to obtain PCN-224-Ca O₂-HA.PCN-224-Ca O₂-HA slowly reacted with H₂O or weak acid to produce O₂ in sufficient quantities,solving the hypoxia problem and enhancing the efficacy of PDT.In addition,HA can protect the Ca O₂ and specifically target the CD44 receptor,which is highly expressed on the tumor cell membranes of 4T1 and MCF-7 cells,realizing targeted therapy.PCN-224-Ca O₂-HA can effectively induce apoptosis of 4T1 and MCF-7 tumor cells after in vitro photodynamic therapy.In vivo,PCN-224-Ca O₂-HA showed significant tumor inhibition,demonstrating that the oxygen generation in situ system can effectively enhanced and targeted PDT.