Application Of Targeted Multifunctional Nanomaterials In Diagnosis And Treatment Of Bladder Cancer

Background:Bladder cancer is the tenth most common malignant tumor.But the effect of clinical treatment has not reached the ideal expectation at present.and the development of nanotechnology may provide new therapeutic methods.Objectives:To detect the efficiency of targeted multifunctional nanomaterials with the functions of magnetic resonance imaging（MRI）,chemotherapy and photothermal therapy（PTT）for the diagnosis and treatment of bladder cancer.Methods:Folate-modified vincristine-loaded polydopamine-coated Fe₃O₄superparticles（Fe₃O₄@PDA-VCR-FA SPs）with MRI,chemotherapy and PTT were developed.The size,stability,photothermal properties,MRI and drug release tests were performed.Cytotoxicity studies and thermo-chemotherapy effect in vitro were assessed by CCK-8 assay and flow cytometry.A Balb/c nude mice model was established by subcutaneous injection of T24 cells.A thermal camera was used to record the increases of temperature at the tumor sites.T₂-Weighted MRI was used to investigate the targeting diagnostic capability of Fe₃O₄@PDA-VCR-FA SPs.Inductively coupled plasma atomic emission spectroscopy（ICP-AES）was employed to evaluate the pharmacokinetics and biodistribution.Assays for serum glucose,serum lipid and hepatorenal functions were used to evaluate the short-term toxicity.H&E stained histopathological slices of vital organs and tissues（heart,liver,spleen,lung,kidney and bladder tumors）were used to evaluate the biosafety and therapeutic effect on bladder cancer.Results:The prepared Fe₃O₄@PDA-VCR-FA SPs was spherical,which average hydration particle diameter was 133.87±1.04 nm.The zeta potential of Fe₃O₄@PDA-VCR-FA SPs was-35.2±2.8 m V.The negative charge on the surface of materials can make it steadily dispersible in aqueous solution.The photothermal conversion efficiency of Fe₃O₄@PDA-VCR-FA SPs was calculated as 55.5%.And the transverse relaxation rate（r₂）was measured as 210.91 m M^-1 s^-1,making it useful for tumor diagnosis as a T₂-weighted MRI contrast agent.The loading ratio of Fe₃O₄@PDA-VCR was calculated to be 19.3%and VCR loaded in the PDA shell can be released under the stimulation of an acidic tumor microenvironment and NIR laser to accomplish chemotherapy.Cellular experiment in vitro showed that the SPs had a significant damage effect on T24 cells.The half-life of Fe₃O₄@PDA-VCR-FA SPs in blood was calculated as 2.83 h,and the tumor retention rate was 5.96%ID g^-1.The tumor site temperature reached 54.4 degrees after 12 min of 0.33 W/cm²laser irradiation.Blood tests and histological slices of the major organs confirmed that Fe₃O₄@PDA-VCR-FA SPs showed good biosafety.Fe₃O₄@PDA-VCR-FA can be used in T₂-weight MRI in vivo.Further combining an 808 nm NIR laser,under the synergistic effect of MRI,photothermal therapy and chemotherapy,the multi-functional diagnosis and treatment of bladder cancer had been successfully implemented.Conclusion:1.Combined with the targeting effect of folic acid,the biological utilization rate of Fe₃O₄@PDA-VCR-FA SPs was greatly improved and the toxicity was effectively reduced.2.Fe₃O₄@PDA-VCR-FA SPs can serve as an excellent contrast agent in T₂-weighted MRI.3.Under the synergistic effect of photothermal therapy and chemotherapy,bladder tumors were completely ablated,and no recurrence was observed.