| Background:Bladder cancer is the second most prevalent malignancy of the urogenital system,and its clinical diagnosis and treatment have not progressed significantly for many years;emerging nanotechnology and nanotechnologies will provide innovative methods of diagnosis and treatment.Objectives:To investigate the effect of Fe(?)-doped polyaminopyrrole nanoparticles(FePPy-NH2 NPs)in photothermal treatment of bladder cancer under dual-mode imaging-guided of photoacoustic imaging(PAI)and magnetic resonance imaging(MRI).Methods:FePPy-NH2 NPs with MRI,PAI,and PTT functions were prepared by oxidative polymerization reaction using ferric ion and aminopyrrole monomer(Py-NH2)at different molar ratios.The morphology,particle size,UV absorption value,and ferric ion loading rate of the prepared nanoparticles were determined by basic chemical characterization,and 6:1 was selected as the optimal molar ratio and was consistently used for the subsequent experiments.Then,the photothermal properties,colloidal stability,PAI and MRI properties of the nanoparticles at the6:1 molar ratio were determined.Evaluation of the cytotoxicity of FePPy-NH2 NPs and in vitro photothermal treatment by CCK-8 assay and flow cytometry to evaluate the toxicity of the nanoparticles to normal cells and their ability to kill T24 cells.A balb/c nude mouse T24 bladder cancer model was established,and in vivo photothermal treatment experiments were performed using an 808 nm NIR laser at 0.33 W/cm~2 under the guidance of dual-mode imaging of MRI and PAI,while the warming of the cancer region was monitored using an infrared camera.The short-term cellular biotoxicity of the nanoparticles was assessed by analyzing the liver and kidney function indexes of each group of nude mice,and the pharmacokinetics and in vivo tissue distribution of the nanoparticles were analyzed by inductively coupled plasma atomic emission spectroscopy(ICP-AES).The biosafety of the nanoparticles and the effectiveness of photothermal therapy on bladder cancer were investigated by comparing H?E stained sections of vital tissues and organs(heart,liver,spleen,lung and kidney)and cancerous tissues.Results:We prepared FePPy-NH2 NPs with excellent MRI,PAI,and PTT properties.The FePPy-NH2 NPs at a 6:1 molar ratio were spherical and homogeneous in size,with an iron ion loading of 18%,a photothermal conversion efficiency of 44.3%,and a longitudinal relaxation rate(r1)of 1.03 m M-1.s-1.In vitro cellular experiments showed that the FePPy-NH2 NPs showed low cytotoxicity to normal cells(Ealy926)and significant killing effect on T24 cells.In vivo animal experiments,the circulating half-life of FePPy-NH2 NPs was 7.59±0.45 h,and the retention rate in the cancer region was 5.07±0.09%ID/g.The MRI and PAI images of FePPy-NH2 NPs similarly confirmed the enrichment of nanoparticles in the cancer region.After 32 min of irradiation with a 0.33 W/cm~2 808 nm NIR laser under dual-mode imaging guidance,the temperature of the cancer region reached 60°C and the bladder cancer was completely eliminated with no recurrence.Hematological monitoring and H?E-stained sections of major organ tissues confirmed that FePPy-NH2 NPs had a good biological safety.Conclusion:1.FePPy-NH2 NPs have a long blood circulation half-life and high enrichment rate in the cancer region,which can effectively enhance the bioavailability of nanoparticles and thus the imaging and therapeutic effects.2.FePPy-NH2 NPs have dual-mode imaging performance of MRI and PAI,which can precisely localize the cancer location and thus guide the PTT of bladder cancer.3.FePPy-NH2 NPs have excellent photothermal therapeutic effect,which effectively achieves complete removal of bladder cancer under the guidance of dual-mode imaging. |
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