Preparation Of Conjugated Polymer With High NIR-Ⅱ Fluorescence Brightness And NIR-Ⅱ Photothermal Therapy In Tumor

Compared with near-infrared-Ⅰ region(NIR-Ⅰ,700-1000 nm)optical imaging,near-infrared-II region(NIR-Ⅱ,1000-1700 nm)optical imaging exhibited deeper penetration depth,higher signal-to-noise ratio.However,it is still a big challenge to combine the NIR-Ⅱ fluorescence imaging(FI),NIR-Ⅱ photoacoustic imaging(PAI),and NIR-Ⅱ photothermal therapy(PTT)effectively to achieve real-time NIR-Ⅱ imaging-guided precision treatment of tumors through molecular engineering.Herein,conjugated polymers with high NIR-Ⅱ fluorescence brightness and NIR-Ⅱ photothermal performance were firstly synthesized by varying the conformation and bulk of alkyl chains from donor unit.The electron acceptor density of conjugated polymers was modulated subsequently,a conjugated polymer with NIR-Ⅱ fluorescent emission,photoacoustic signaling and photothermal therapeutic properties was screened and used for efficient treatment of in situ osteosarcoma with bimodal optical imaging guidance.The main contents of this paper are as follows:(1)Preparation of high-brightness NIR-Ⅱ fluorescent conjugated polymers by side conformation regulation and application in NIR-Ⅱ photothermal antitumor therapy.Conjugated polymer possess narrow energy gap and strong non-radiative transitions,but the NIR-Ⅱ fluorescence brightness is low.So side-chain engineering strategy is proposed in this chapter to enhance the NIR-Ⅱ fluorescence intensity of conjugated polymers.First,the conjugated polymers P1,P2 and P3 were synthesized,in which thiadiazoloquinoxaline(TQL)was used as the electron acceptor,and different side chain-modified benzodithiophenes(BDT)were applied as electron donors.Then,the effect of conjugated polymer side chain structure conformation and volume on the brightness of NIR-Ⅱ was investigated.Polymer P3 with the highest NIR-Ⅱ fluorescence brightness is screened to fabricate water-dispersible nanoparticles(P3 NPs).Under 1064 nm laser irradiation,P3 NPs demonstrate excellent photothermal performance with high photothermal conversion efficiency(PCE)up to 33.42%.In vivo imaging of mice showed that under 808 nm laser excitation,NIR-Ⅱ vascular imaging with a high signal-to-background noise ratio(SBR)can be achieved,and SBR is up to 4.81.In addition,under the guidance of NIR-Ⅱ fluorescence imaging,NIR-Ⅱ anti-tumor therapy in tumor mouse was realized.(2)Preparation of high-brightness NIR-Ⅱ fluorescent conjugated polymers regulated by regulating acceptor density and application in NIR-Ⅱ photothermal therapy for in-situ osteosarcoma.Firstly,4,8-Bis(5-bromo-4-(2-octyldodecyl)thiophen-2-yl)-benzo[1,2-c;4,5-c’]bis[1,2,5]thiadiazole(BBT)was used as the electron acceptor,4,7-Bis(2-3Me Sn-5-thienyl)-2,1,3-benzothiadiazole(BT)and 4,4’-di-n-dodecyl-2,2’-bithiophene(2TC)was used as electron donors,a series of conjugated polymers with different receptor densities was prepared by regulating the proportion of different donor units.This group of polymers was tested and compared to screen for conjugated polymer P2 with both high NIR-Ⅱ absorption and NIR-Ⅱ emission.Subsequently,P2 is prepared into water-dispersible nanoparticles(P2 NPs)for in vitro optical experiments.Under 1064 nm laser irradiation,the photothermal conversion efficiency of P2 NPs was measured to be 38.8%.The photoacoustic signal intensity of P2 NPs is linearly related to the concentration of nanoparticles under the irradiation of 1064 nm pulsed laser,so that P2 NPs exhibited excellent photoacoustic imaging ability.The result in vitro demonstrated that P2 NPs show great potential in vivo NIR-Ⅱ optical imaging and NIR-Ⅱ photothermal therapy.Finally,Under 808 nm laser irradiation,the SBR of NIR-Ⅱ fluorescence imaging of hind limb blood vessels in tumor mice reached 7.3,and achieved high-quality NIR-Ⅱ fluorescent/photoacoustic bimodal imaging-guided photothermal therapy in vivo subcutaneous and in situ osteosarcoma models.