| Anaplastic thyroid carcinoma(ATC)is one of the most aggressive malignant tumors with poor prognosis.Due to the lack of effective diagnosis and effective therapy,the mean survival time of ATC is only 4.2 months.Therefore,it is extremely urgent to explore new methods of diagnosis and therapy against ATC.Multi-functional drug-loaded nanoparticles have received extensive attention and research in the field of the theranostic of tumors.On the one hand,the tumor is located and monitored by the enhanced imaging.On the other hand,the drugs are released by the internal or external stimulation,which enhanced the diagnostic accuracy and efficacy of the disease.This study is divided into three parts.Firstly,the targeted drug-loaded phase-changeable nanoparticles(C-HPNs)were fabricated,and their basic physicochemical properties were detected.The ultrasound imaging capability,the targeting ability and the cytotoxicity of C-HPNs were detected by a series of experiments in vivo and in vitro.This study provides a new theranostic strategy and research basis for anaplastic thyroid carcinoma.Objectives To prepare C225-modified targeted 10-HCPT loaded phase-changeable nanoparticles,to detect their physicochemical properties,the imaging ability,targeting ability and therapeutic effect in vitro and in vivo.Methods C-HPNs were successfully prepared by double emulsion method and carbodiimide method.The basic properties were tested,including the morphology,particle size,stability,thermotropic phase transition,connection efficiency,UV absorption characteristics,drug entrapment rate and release profile by LIFU in vitro.The optimal LIFU parameters of ADV of C-HPNs were studied,and the binding of nanoparticles and cells in each group was detected.CCK-8 method was used to detect the cell viability,and the effects of 10-HCPT solution and different nanoparticles on cell viability with or without LIFU irradiation were detected.The effects of C-HPNs +LIFU on apoptosis and cell cycle of C643 cells were detected by FCM.The in vivo biosafety of C-HPNs was first tested.The imaging capabilities were studied using a small animal in vivo imaging system and FLCM.Ultrasound images of each group before and after LIFU irradiation were detected.The tumor growth curve was drawn.After the treatment,the tumor mass was weighed,and the tumor inhibition rate(TIR)was calculated,the pathological detection,cell proliferation and apoptosis,and the biological toxicity was detected.Results The C-HPNs were successfully prepared.The TEM showed a typical core-shell structure.The particle size and potential of C-HPNs were 241±4.04 nm and-3.28±0.91 m V,respectively.C-HPNs showed good stability and thermotropic phase changeable ability;C225 were successfully coupled,the connection rate was 91.3 ± 1.8%;the EE and LE of 10-HCPT were 73.76 ± 12.1%,6.39 ± 1.49%,respectively.LIFU could significantly promote the drug release in vitro.The LIFU parameter for the C-HPNs ADV is preferably 6W,3min.The C-HPNs +LIFU group showed good active targeting in vitro.After LIFU irradiation,the C-HPNs + LIFU group had the lowest cell activity,the highest the G1 phase block rate and total apoptotic rate.C-HPNs showed good biosafety and active targeting in vivo,and LIFU could promote the aggregation of C-HPNs in tumor sites.C-HPNs could enhanced ultrasound imaging in vivo.In the in vivo therapeutic experiment,the C-HPNs + LIFU group had the largest TIR,the most severe cell destruction,the mostapoptotic cells,and the least proliferating cells.The 10-HCPT group and the10-HCPT+LIFU group had the lowest white blood cell counts and the highest ALT and BUN.Conclusion C225-modified phase-change nanoparticles containing10-HCPT were successfully prepared.C-HPNs have good biosafety and active targeting ability in vivo.Combined with LIFU,it can enhance the ultrasound imaging in vitro and in vivo.The therapeutic effect of subcutaneous xenografts is expected to open up new ideas for the diagnosis and treatment of ATC. |
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