Preparation Of Novel Molecular Probe Polipo-IR And The Study Of Diganosis And Treatment Of Photoacoustic And Photothermal On Nude Mice Bearing Hepatic Carcinoma

BackgroundHepatic carcinoma(HCC)is the sixth most common tumor in the world and the third most common cause of cancer-related death.The overall 5-year survival rate of HCC is less than 30%,mainly due to the lack of the effective method for accurate preoperative diagnosis and navigation surgical resection.Photoacoustic molecular imaging(PMI)technology combines the merits of large penetration depth of photoacoustic imaging,the high sensitivity of optical imaging and the advantages of exogenous molecular probes with wihch strong optical signal components and the good targeting ability,and it has a broad application prospect in the diagnosis of HCC with which deeper location and rich blood supply.However,the currently reported absorption bands of exogenous molecular probes are mainly located in the first near-infrared region(NIR-I:650-900 nm)and most of them are metal nanoparticles,carbon and other inorganic materials with which poor long-term biological safety.IR-1061 dye is an organic small molecule dye whose absorption band is located in the second near-infrared region(NIR-?:1000-1350 nm).Compared with NIR-?,NIR-?molecular probes possess longer imaging wavelength and better penetration depth.IR-1061 dye has no obvious cytotoxicity in its free form.As a polymethylacetylene dye,its absorption peak value may be shifted red or blue after the arrangement change of dye molecules.In addition,IR-1061 is insoluble in water.The fluorescence quantum yield is only 1.7%,so it may have high photothermal conversion efficiency(PCE).ObjectiveIn this study,IR-1061 dyes were encapsulated into the nanocarrier by a scientific method to improve its water solubility,and explore whether the obtained nanoparticle has higher PCE in NIR-II,and study the abilities of PA diagnosis,surgical navigation and photothermal treatment(PTT)of HCC.MethodThe small molecular dye(IR-1061)-loaded lipid nanoparticles(Polipo-IR NPs)were synthesized by these steps:Firstly,IR-1061 dyes,cholesterol(CH)and 1,2-distearoyl-sn-glycero-3-phosphocholine(DSPC)were dissolved in dichloromethane and dispersed by supersonic vibration.Then,IR-1061 dyes were encapsulated in the liposomes by rotatory evaporation method,and the nanoparticles were modified by DSPE-PEG2000.The morphology,zeta potential,size,photoacoustic signal,photoacoustic stability,photothermal effect,PCE,cytotoxicity,hemolysis experiment of the obtained nanoparticles were investigated through the in vitro experiment.The studies of photoacoustic preoperative diagnosis,surgical navigation and PTT on nude mice bearing HCC were further investigated.ResultsPolipo-IR NPs,a novel organic small molecule probe developed in this study.The hydrodynamic diameter is about 65.8 nm,and the zeta potential is-12.8 mv.The Polipo-IR NPs possess ultrasensitive photoacoustic signal and high PCE(45.25%).The excellent photostability,good water-solubility and high biocompatibility were all validated by in vitro and in vivo experiments.The in vivo photoacousrtic studies in mice bearing orthotopic HCC demonstrated that Polipo-IR NPs can non-invasively and accurately diagnosis tumor preoperatively with a signal-to-noise ratio(SNR)of 5.98±0.23 at 3 h post-injection and could successfully achieve radical resection of tumor intraoperatively.Furthermore,the PTT test demonstrated a remarkable cancer cell killing ability because of its high PCE.ConclusionThe outcomes showed that the nanoparticles(Polipo-IR NPs)possess appropriate size,good biocompatibility,high PCE,ultrasensitive photoacoustic signal.The outcomes firstly demonstrated the well application of photoacoustic diagnosis,surgical navigation and PTT of IR-1061 dye-based nanoparticles for HCC and provided novel insights towards understanding polymethine dyes in nanomedicine.