Colorectal cancer(CRC)is the third most common malignancy worldwide and has the second-highest cancer mortality rate.Chemotherapy remains the primary treatment for patients with advanced CRC,and the high abundance of Fusobacterium nucleatum(Fn)at CRC sites has led to resistance to the chemotherapeutic agent Oxaliplatin(Ox Pt).In addition,Fn tends to produce biofilm,which not only protects the bacteria to promote adhesion and growth but also leads to reduced sensitivity of tumor cells to anti-cancer drugs,making chemotherapy more difficult.On the other hand,in traditional strategies against tumors,diagnosis,and treatment are independent of each other,which leads to difficulties in precise control during the treatment and monitoring of tumors.Therefore,there is a need to eliminate Fn and thus resistance to chemotherapeutic drugs during chemotherapy,while achieving more precise and effective antitumor efficacy with integrated diagnosis and treatment.To this end,we introduced carboxylated oxaliplatin(Ox Pt-COOH)and the antimicrobial agent lauric acid(LA)into hyperbranched glycidyl ether(PG)and formed O-SPIONs@PG-Pt-LA nano micelles by self-assembly with oleic acid-modified iron oxide nanoparticles(O-SPIONs)to combine chemotherapy with chemodynamic therapy to overcome chemoresistance and achieve therapeutic integration.Dynamic light scattering(DLS)and scanning electron microscopy(SEM)have shown that the nano micelles have a particle size of about 200 nm and can enrich the tumor site through enhanced penetration and retention(EPR)effects.Drug release experiments showed that the nano micelles had high drug loading capacity and a reduction-stimulated response in p H and GSH.3,3’,5,5’-Tetramethylbenzidine(TMB)color development experiments confirmed the peroxidase activity of the system.The good antibacterial properties of nano micelles against Fn were verified by the coating plate method and crystalline violet staining,and LA and O-SPIONs had synergistic antibacterial effects.In vitro cell experiments showed that O-SPIONs@PG-Pt-LA could be taken up by cells with good biocompatibility,and the nano micelles could trigger the Fenton reaction,which increased the intracellular ROS and MDA content and induced cellular iron death.In vivo,animal experiments have demonstrated the superior imaging and antitumor effects of O-SPIONs@PG-Pt-LA with a high biosafety profile.This chemokinetic therapy,in synergy with antimicrobial agents to improve the antimicrobial properties of the material on the one hand,and chemotherapy improves its antitumor activity on the other hand,thus fundamentally solving the drug resistance problem of Ox Pt caused by Fn and providing real-time monitoring and evaluation of the therapeutic process,provides new ideas for the construction and clinical translation of efficient antitumor drug carriers. |