Tunable Nanoparticles With Aggregation-Induced Emission Heater For Precise Synergistic Photothermal And Thermodynamic Oral Cancer Therapy Of Patient-Derived Tumor Xenograft

Oral cancer is a common head and neck cancer.Its pathogenesis is closely related to diet and health habits in addition to environmental and genetic factors.The traditional treatment of oral cancer mainly includes chemotherapy,surgery and radiotherapy.However,the three cancer therapies mentioned above have some defects and deficiencies in the clinical treatment process.Therefore,it is particularly important to develop safe and efficient new cancer therapies to improve the living conditions and quality of life of patients.Cancer thermotherapy is a new method of non-invasive treatment for cancer.Photothermal therapy(PTT)and thermodynamic therapy(TDT)are two important methods in cancer hyperthermia.The combination of PTT and TDT,combined with fluorescence imaging(FLI)technology,can produce photothermal effect and carbon free radicals at the tumor site,and realize real-time monitoring to play an excellent anti-tumor effect.However,the common aggregation of traditional fluorescent materials leads to fluorescence quenching(ACQ),which degrades their sensitivity and luminescent properties.In order to overcome the defect of ACQ fluorophore,aggregation induced luminescence(AIE)fluorophore came into being.It is highly respected in biological imaging because of its advantages,such as intense luminescence in the aggregation state,photobleaching tolerance,and large Stokes shift.In this study,a kind of AIE molecule with NIR II FLI performance and a new azo polymer were synthesized.By self-assembly of the two,a nanosystem with NIRⅡ fluorescence imaging performance was prepared,which could be used for PTT/TDT collaborative treatment of cancer(NMB@NPs).The thermodynamic nanoparticle has a diameter of about 70 nm and excellent particle size and size distribution.At the same time,it has excellent photothermal physical properties and can be decomposed by the heat generation induced by the photothermal effect to produce carbon-free radicals.In vitro anti-tumor efficacy,the experiment revealed that the combination of the photothermal effect of NMB@NPs and free radicals produced could effectively kill cancer cells.Sequencing results of whole genome RNA expression showed that most genes specifically expressed in NMB@NPs nanoparticles(+laser)were attributed to the synergistic effect of photothermal therapy and carbon free radicals,respectively.Imaging experiments prove that NMB@NPs have excellent tumor imaging and photothermal imaging functions and can be used for real-time tracking and photothermal therapy of tumors.In vivo tumor inhibition experiment confirmed that NMB@NPs plus NIR group could trigger tumor cell apoptosis and showed a significantly better anti-tumor effect on the PDX model of oral cancer.Finally,the biocompatibility of NMB@NPs nanoparticles was studied by HE staining,hemolysis analysis,blood routine,and biochemical analysis,and the results showed that it had good biocompatibility.In conclusion,this synergistic photothermal and thermodynamic strategy based on AIE luminous agent brings new insights to advanced multifunctional fluorescent nanoparticles designed for precise biomedical applications and is expected to improve the therapeutic effect of cancer.