The Study Of A Novel Organic Photosensitizer PBDB-T Inducing Immunogenic Cell Death In Oral Squamous Cell Carcinoma

[Objective] To explore the effect and mechanism of a novel organic photosensitizer PBDB-T in inducing immunogenic cell death in oral squamous cell carcinoma.[Methods] PBDB-T nanoparticles(PBDB-T NPs)were prepared through nano coprecipitation method.The morphology and particle size of PBDB-T NPs were analyzed by transmission electron microscopy(TEM)and dynamic light scattering(DLS).UV-vis-NIR spectrophotometer and photoluminescence spectrometer were used to analyze the ultraviolet-visible(UV-vis)spectrum and the fluorescence spectrum of PBDB-T NPs,respectively.PBDB-T NPs were dispersed in mimic physiological fluid to evaluate their biological stability.Measurement of photothermal performance and photothermal stability was carried out under laser irradiation.Anti-tumor effect of PBDB-T NPs’ photothermal effect was detected by CCK-8 and Live/Dead Cell Double Staining in cell experiment,and further assessed in OSCC Xenograft models.The controllability of the photothermal properties of PBDB-T NPs was evaluated by adjusting the laser power and the concentration of nanoparticles.Based on this,the therapeutic procedure of PBDB-T NPs PTT was strictly designed to precisely control treatment temperature.The photothermal killing effect and immunogenicity of programmed mild PTT were further evaluated.At last,tumor bearing mice models were established to evaluate the immunogenicity and immune activation of programmed mild PTT mediated by PBDB-T NPs.[Results] Organic nanoparticles PBDB-T NPs,which had a uniform and spheroidal appearance in an aqueous solution,with an average diameter approximately at 165 nm,were successfully synthesized and prepared.Meanwhile,it obtained outstanding biological stability in mimic physiological fluids.The UV-vis spectrum of PBDB-T NPs exhibited peaks at 631 nm.Furthermore,in the fluorescence emission of PBDB-T NPs,a prominent peak was observed at approximately 691 nm,suggesting that PBDBT NPs could be employed in NIR-I imaging.With a photo-heat conversion efficiency(PCE)of around 40%,PBDB-T NPs PTT had been proved to have excellent anti-tumor effect and biosafety in vivo and in vitro.Further studies showed that the photothermal properties of PBDB-T NPs could be highly controlled by adjusting the concentration of nanoparticles and the laser power.Moreover,the treatment temperature was accurately controlled at 40℃,42℃ and 45℃ by strictly developing illumination procedures.Cell experiments confirmed that programmed mild PTT enhanced anti-tumor effect significantly.After 3 times of PTT at 42℃,>60% of tumor cells were damaged.At the same time,programmed mild PTT could significantly upregulate damage associated molecular patterns(DAMPs),e.g.calreticulin and high mobility group proteins B1,and achieve adjustable immunogenicity.PTT at 42 ℃ for 3 times could obtain the maximum release of DAMPs,which mediated best immune activation effect and achieved 3/8 tumor free rate and maximum tumor growth inhibition effect in tumor bearing mice model.[Conclusion] Novel organic nanoparticles PBDB-T NPs,characterized with outstanding biocompatibility and biosafety,stable and gorgeous photothermal conversion efficiency,were successfully prepared,and could achieve excellent anti-tumor effect in vitro and in vivo.Mild PTT could be achieved by programmed therapy.Based on programmed mild PTT mediated by PBDB-T NPs,exciting high tumor killing effect and optimal immune activation could be realized.Our research provided guidance for PBDB-T biomedical application,mild photothermal treatment and development of photothermal treatment procedure.