| Background To study the effectiveness of PDA@HMONs-DOX/PFP(PHDP)nanoparticle in the integration of breast cancer diagnosis and treatment,and to explore its biocompatibility and degradation,collaborative treatment of near infrared ray(NIR)high induced liquid gas phase change and function of synchronous ultrasound imaging,so as to build a real-time ultrasound-guided breast cancer high-efficiency chemotherapy and photothermal collaborative diagnosis and treatment platform.Methods According to the"chemical homology"mechanism,the hollow mesoporous organosilicon nanoparticles(HMONs)modified by polydopamine(PDA)were prepared as carriers,which were loaded with DOX and PFP.Transmission electron microscopy,N2 adsorption analyzer,Zeta potential detection,dynamic light scattering,magnetic resonance spectroscopy,UV-Vis spectrophotometer was used to characterize the samples;Extracellular drug release of DOX was detected by dialysis;Bubble release and ultrasonic imaging was detected by optical microscope and ultrasonic diagnostic instrument;In cell experiments,MTT method was used to evaluate the cytotoxicity of PHDP;transmission electron microscopy,flow cytometry and inductively coupled plasma atomic emission spectrometry(ICP-OES)were used to detect the cell uptake behavior of PHDP nanoparticles;after NIR irradiation,enzyme scale instrument was used to detect,and according to the optical density(OD)calculate the cell activity to evaluate the synergistic treatment effect.Cell viability was observed by calcein AM/PI staining.The tumor model of breast cancer in nude mice was established.The model was divided into five groups:control group;DOX group;PHDP group;PDA@HMONs PFP combined with NIR group;PHDP combined with NIR group.The biodistribution and biosafety of PHDP were evaluated;the tumor suppression effect was analyzed and the apoptosis of tumor cells was detected.The tumor was observed and imaged by ultrasound.Results HMONs particles were successfully synthesized in this study.The average particle size was 75 nm,the specific surface area was about 835.1 m~2/g,and the pore diameter was about 3.64 nm.In vitro simulation liquid(high GSH),it was found that HMONs particles were completely dissolved after one-week observation.Based on HMONs particles,PHDP nano diagnostic and therapeutic system with an average particle size of 125.1nm was constructed based on HMONs particles.It has a good colloidal stability,drug loading of 328mg/g,and effective release of DOX under the dual stimulation of p H/GSH.PHDP nanocomposites have good photothermal conversion properties,and liquid-gas phase transition occurs under the irradiation of near-infrared light in vitro.There is a significant difference in ultrasonic signal between gray-scale mode and contrast mode(P<0.05).The amount of silicon absorbed by PHDP nanoparticles was significantly increased after 2 hours,4 hours and 8 hours(P<0.05);the amount of DOX absorbed by PHDP nanoparticles was more than that of free DOX,the difference was statistically significant(P<0.01);the degradation of PHDP was observed by transmission electron microscopy after 4 days.The apoptosis rate of cells was dramatically enhanced by PHDP combined with near-infrared irradiation.(P<0.01).In vivo experiments demonstrated that PHDP combined with NIR group had the most significant tumor inhibition compared with the other four groups(P<0.01).At the same time,biosafety analysis showed that there was no obvious necrosis in the main organs of nude mice.PHDP nano diagnostic and therapeutic system in vitro and in nude mice,after irradiation by NIR,can achieve ultrasound imaging.Conclusion Therefore,such“all-in-one”PHDP nanoparticles with satisfactory biocompatibility and biodegradability,hyperthermia-induced bubble ability and simultaneous US imaging performance hold great potential for cancer nanotheranostics. |
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