Research On The Design And Synthesis Of Near-Infrared Multiple Cyanide Acceptors Organic AIE Compounds And Their Application In Bioimaging And Photodynamic/Photothermal Therapy

Photodynamic therapy(PDT)uses light-activated photosensitizers(PS)to generate toxic reactive oxygen species(ROS)that cause tumor cell death through peroxidation of lipids,proteins,DNA,and RNA.Photothermal therapy(PTT)uses photothermal reagents to convert absorbed light into heat,causing an increase in temperature around the tumor tissue,leading to intolerable cell death.PDT and PTT have become attractive strategies in clinical cancer treatment due to their advantages of low invasiveness,low side effects,and good selectivity.However,the combination of PDT and PTT is considered a more desirable strategy in the field of optical therapy because the best therapeutic results are often not obtained with a single therapy.In this paper,we designed and synthesized organic aggregation-induced luminescence(AIE)compounds with near-infrared absorption,which can generate ROS under light excitation to achieve PDT,or convert the absorbed light energy into heat energy while generating reactive oxygen species to achieve synergistic therapy with PDT and PTT.The main work of the paper is divided into two parts.Part Ⅰ:We propose a molecular design strategy to enhance the interaction between the donor(D)and the acceptor(A)by enhancing the electron-absorbing accceptor and expanding the π-conjugated planar unit to induce the compound to absorb and emit red-shift.In this part,a novel D-A-π-A Schiff base 5-(((5-(7-(4-(diphenylamino)phenyl)-benzo[c][1,2,5]thiadiazol-4-yl)thiophen-2-yl)me thylene)amino)-3-methylthiophene-2,4-dicarbonitrile(TBTDC)was synthesized using triphenylamine as the donor,benzothiadiazole,cyanothiophene as the acceptor,and thiophene as the linking unit.Due to the distorted molecular structure of the triphenylamine unit,the compound exhibited AIE properties.Luminescence wavelength was located in the near-infrared region with a large Stokes shift(300 nm).After co-precipitation with F-127 to form nanoparticles(NPs),their fluorescence wavelength is 825 nm,with excellent cellular fluorescence imaging and two-photon imaging,and the two-photon imaging tissue penetration depth can reach 300 μm.Moreover,TBTDC NPs have excellent photostability,good biocompatibility can specifically target lysosomes,and the energy level difference(ΔEST)value between the triplet state and the singlet state is Further in vitro and in vivo experiments showed that TBTDC NPs have significant PDT therapeutic effects and can effectively inhibit tumor growth without physiological toxicity in all physiological indicators after treatment.The experimental results suggest that TBTDC NPs can be used as near-infrared fluorescent nanoprobes with promising applications in the fields of bioimaging and targeted PDT therapy.Part Ⅱ:The AIE photosensitizers TBD,MeTBD,TBDD with A-π-D-π-A structures with PDT/PTT synergy were designed and synthesized using triphenylamine or 4’,4’-dimethoxytriphenylamine as the electron donor,1,3-bis(dicyandiylmethyl)indene as the electron acceptor,and benzene ring or thiophene as the π-bridge.They have good absorption(～600 nm)and emission region in NIR Ⅱ(>900 nm)region.And more importantly,they have both photodynamic and photothermal effects.Theoretical calculations show that they have a narrow band gap with a small ΔEST,and experiments showed that the compounds TBD,MeTBD and ThBD have good photothermal conversion ability and reactive oxygen generation efficiency.The compounds were prepared into nanoparticles with excellent photostability and good biocompatibility.The potential of these compounds as type Ⅰ and Ⅱ photodynamic photosensitizers was demonstrated by ABDA,HPF and DCFH as ROS indicators;good photothermal conversion and cycling performance and photoacoustic imaging were achieved.In vitro experiments further confirmed that ThBD NPs with excellent biocompatibility exhibited superior antitumor therapeutic effects under white light and 660 nm laser irradiation,and the combination treatment did significantly induce apoptosis and inhibit the proliferation of tumor cells.These experimental results suggest that this class of compounds has great potential to be developed into a single molecule system for multimodal imaging-guided PDT/PTT combination therapy.