Early and accurate cancer diagnosis can dramatically increase the overall survival rate and decrease patients’suffering,and once cancer was detected and diagnosed,treatment in time is vital for the successful cure of the disease.Photothermal therapy(PTT),which utilizes heat generated from optical energy to ablate cancer cells with high anticancer efficiency,is an ideal therapeutic modality for cancer treatment.Benefiting from the strong tissue penetration of light in near-infrared(NIR)region(700–900 nm),photothermal agents(PTAs)with absorbance in the NIR region are highly promising to improve the therapeutic outcome of PTT.On the other hand,the subcellular localization of PTAs in cancer cells is also important to realize effective treatment.Mitochondria as the powerhouses of cells are indispensable for cell survival.Besides,mitochondria play a key role in modulating the process of cell apoptosis.Thus,mitochondria have served as an ideal target for cancer therapy.Because mitochondria are highly sensitive to reactive oxygen species and hyperthermia,developing mitochondria-specific reagents for simultaneous targeting,imaging,and treatment is highly desirable in cancer theranostics.Herein,we synthesized a series of NIR-absorbing heptamethine dyes and fabricated two nanomicelles via covalent conjugation or physical encapsulation for tumor PTT.Besides,a highly efficient and safe antibacterial agent based on NIR-emitting water-soluble quaternized cyanine dye with on-demand clearable property was also developed.The detail research works are listed as below:1.Dual channel activatable cyanine dye for mitochondrial imaging and mitochondria-targeted cancer theranostics:IR825-Cl,which possesses two separated excitation wavelength channels for both red fluorescence imaging and NIR photothermal therapy(PTT),is a mitochondria targeted cyanine dye.For imaging,IR825-Cl had a turn-on response of red fluorescence(610 nm)in mitochondria under 552 nm excitation due to its solvent polarity-responsive fluorescence emission,and it served as a wash-free red-emitting fluorescent probe for mitochondria imaging.Moreover,IR825-Cl realized the selective mitochondrial staining of cancer cells over normal cells and thus served as an ideal fluorescent probe for identifying cancer cells in normal tissues,which is extremely beneficial for cancer theranostics.For PTT,under 808 nm NIR laser irradiation,IR825-Cl efficiently converted optical energy into heat(its light-to-heat conversion is 17.4%),realizing mitochondria-targeted photothermal cancer therapy.2.Turning double hydrophilic into amphiphilic:IR825-conjugated polymeric nanomicelles for NIR fluorescence imaging-guided photothermal cancer therapy:Herein,a novel photothermal agent(PTA)was innovatively constructed by conjugating the hydrophobic IR825-NH2 with a double hydrophilic block copolymer PEG-PLD.The PEG-PLD(IR825)was amphiphilic and could self-assemble into polymeric nanomicelles in aqueous solutions.The PEG-PLD(IR825)nanomicelles with high drug loading rate(~21.0%),long blood circulation time in vivo(its half-lives is 15.2 h),negligible premature release of IR825 during systemic circulation,and high NIR light-to-heat conversion efficiency(17.4%).Besides,PEG-PLD(IR825)nanomicelles showed solvent polarity-sensitive fluorescence at~610 nm(under 552 nm excitation)and 830nm(under 780 nm excitation),which was especially useful for both in vitro visible fluorescence imaging and in vivo NIR fluorescence imaging-guided photothermal therapy(PTT).The PEG-PLD(IR825)nanomicelles showed high PTT efficacy both in vitro and in vivo.More importantly,the PEG-PLD(IR825)nanomicelles underwent degradation after laser irradiation,which ensured their post-treatment biosafety.3.Cyanine-containing polymeric nanoparticles with imaging/therapy-switchable capability for mitochondria-targeted cancer theranostics:Early and accurate diagnosis as well as treatment in time of cancer are extremely important for cancer therapy.Herein,theranostic PF127/me-IR825 nanoparticles(NPs)with inherent mitochondrial targeting/imaging,cancerous/normal cell differentiation capabilities,early-stage cancer diagnostic,and mitochondria-based photothermal therapy(PTT)were developed via physical encapsulation of me-IR825 into the inner core of Pluronic F127(PF127).This NPs showed two fluorescence emissions at610 nm(excited by 550 nm)and 845 nm(excited by 780 nm).The former was used for in vitro mitochondrial fluorescence imaging,cancerous/normal cell differentiation,and early-stage cancer detection with high contrast.The later was used for in vivo NIR fluorescence image-guided PTT.Besides,the as prepared NPs also showed in vivo photoacoustic imaging.Both in vitro and in vivo antitumor therapy results demonstrated that PF127/me-IR825 NPs were highly biocompatible mitochondria-directed photothermal agents for tumor ablation with high efficiency.Besides,me-IR825 inside the inner core of PF127/me-IR825 NPs could be degraded into biocompatible products after PTT treatment,which guaranteed the post-treatment biosafety of the NPs.4.NIR-emitting water-soluble quaternized cyanine dye as a self-traceable and on-demand clearable antibacterial agent:Herein,a NIR absorbing water-soluble quaternized cyanine dye QA-IR825 for antibacterial use was developed.This dye could kill bacteria both in the presence and absence of NIR laser irradiation.Whereas in the presence of NIR laser irradiation,QA-IR825 not only realized a higher antibacterial efficiency,but also enabled photodegradation into non-toxic products,which further guaranteed its biosafety. |