Application Of Targeted Nano-Diagnostic Agents Based On Porphyrin MOFs In Imaging-Guided Cooperative Treatment Of Breast Cancer

Breast cancer is the leading cause of death for women worldwide,and it is also the most expensive malignant tumor for treatment.Chemotherapy or radiotherapy combined with mastectomy is the main treatment method in clinic at present.However,these therapies are exist the risk of failure and usually leave wounds to patients.Photodynamic therapy(PDT)has drawn wide attention in the treatment of breast cancer,because of its high specificity,good curative effect and low side effects.Photodynamic therapy uses photosensitizers to produce singlet oxygen to kill cancer cells in the smallest wound.However,photodynamic therapy can only kill local tumor cells,while residual tumor cells often are a major cause of tumor recurrence.Chemotherapy is one of the most common methods in the treatment of breast cancer,but its clinical application is greatly limited by its serious side effects and drug resistance.Therefore,single treatment method often fails to achieve the best therapeutic effect,while combined treatment can enhance the therapeutic effect with reduced toxic and side effects,which alleviates the pain of patients.In addition,in the course of treatment,due to the lack of synchronization of diagnosis and treatment,it is easy to delay the best treatment opportunity.The use of molecular imaging technology can introduce imaging function to realize the application of integration of diagnosis and treatment in precise cancer therapy.With the rapid development of nanotechnology,nano drug carriers have multiple advantages,which provide a new way for cancer treatment.Metal-Organic Frameworks(MOFs)materials are new porous materials,which have great potential and research value in the field of nano drug carriers.This research is based on the design and synthesis of porphyrin MOFs materials,which integrates image diagnosis and collaborative therapy.Porphyrin MOFs materials themselves can produce singlet oxygen under laser irradiation for photodynamic therapy,and they can carry chemotherapeutic drug oxaliplatin and BSO wihch can sensitize chemotherapy and photodynamic therapy.Therefore,they can synergistically inhibiting the growth of tumor cells.Futhermore,we modified the liposome on the surface of the nanoprobe to improve their biocompatibility and stability,and respectively modified tumor targeting molecules and fluorescent molecules on the lipid surface and the bilayer of lipid.Thus,this nano-diagnostic agent can achieve real-time,accurate diagnosis of the disease and synchronous precise treatment to attain the best therapeutic effect.Based on 4-carboxyphenylporphyrin,PCN MOFs with an average particle size of 90 nm and spherical morphology was prepared by hydrothermal synthesis.In all experiments,4T1 breast cancer cells were selected as tumor cell models.Under 660 nm laser irradiation,the nanomaterial can produce high level of reactive oxygen species.Oxaliplatin and BSO were loaded into nanocarriers at the same time.Cell experiment results showed that BSO could sensitize both chemotherapeutic drugs and photodynamic therapy,so that the nano-diagnostic agent had good killing effect on cancer cells.The results of animal imaging system and fluorescence microscopy demonstrated that the targeted nano-diagnostic agent could highly permeate and retain in the tumor site and enter into tumor cells in larger quantities.By the establishment of mouse tumor model,the results showed that the nano-diagnostic agent plus laser irradiation group can successfully cure tumors.The survival curve and the volume of tumors after treatment further confirmed that the nano-diagnostic agent has a good synergistic therapeutic effect.The results of H&E staining showed that the nano-diagnostic agent had good biocompatibility,so it can safely applied in organisms.This study shows that the targeted nano-diagnostic agent can achieve precise photodynamic/chemotherapeutic synergy under the guidance of fluorescence imaging,and has good synergistic effects.It can promote the apoptosis of cancer cells,remove tumors,avoid recurrence of tumors,and provide a new strategy for the research of integration of diagnosis and treatment of tumors.