Near-infrared Absorbing Organic Small Molecule Nanoparticles For Photoacoustic Imaging And Photothermal Therapy

The near-infrared absorbing organic molecules with a Donor-Acceptor(D-A)structure have broad application prospects as photothermal reagents due to their simple chemical structure,high purity,and good biocompatibility.However,their development is severely limited due to low photothermal conversion efficiency and light instability.Therefore,designing and constructing small organic molecules with near-infrared absorption,high photothermal conversion efficiency and high light stability,and applying them to photoacoustic imaging-mediated photothermal treatment of solid tumors are very important for guiding the diagnosis and treatment of tumor.(1)In this dissertation,by using 2-dicyanomethylene thiazole as an electron-accepting group and triphenylamine as an electron-donating group,a near-infrared absorbing photothermal reagent with D-A structure was constructed.And it was encapsulated in F127 to prepare nanoparticles TPTHM NPs for photoacoustic imaging-mediated photothermal therapy.The prepared organic nanoparticles have uniform particle size(-55 nm),near-infrared absorption,good light stability,high biocompatibility,and high photothermal conversion efficiency(38%).In vitro experiments show that TPTHM NPs can be endocytosed by 4T1 cells,showing strong photoacoustic signals and cancer cell ablation capacity in vitro.Using 4T1 tumor-bearing nude mice as animal models,TPTHM NPs have obvious photoacoustic signal and complete tumor ablation ability in vivo.The experimental results show that TPTHM NPs is a potential candidate for photothermal therapy.(2)Taking heptan-3-yl-2-cyano-2-(4-(4-nitrophenyl)thiazol-2-yl)acetate as the electron acceptor and phenothiazine as the electron donor,a near-infrared absorbing organic molecule C720 with D-A structure was constructed,and its photothermal conversion efficiency was as high as 62%.C720 was then doped in the lipid bilayer,and DOX(doxorubicin)was wrapped in the water core to build C720 and DOX-loaded temperature-sensitive liposomes(CDTSL).The liposomes can achieve NIR laser-controlled drug release for photoacoustic imaging guided chemo-photothermol therapy.CDTSL has fast and controlled drug release characteristics.The results of in vitro and in vivo experiments show that CDTSL has good photoacoustic imaging effects,and its tumor suppressive effect is significantly higher than that of C720-containing temperature-sensitive liposomes(CTSL).Our research provides a promising platform for photoacoustic imaging guided chemical photothermol therapy,and has broad prospects for the diagnosis and treatment of cancer.