The Preparation Of Naphthalocyanine Copper And Gold Nanoparticle Composites For Sonodynamic/Photothermal Synergetic Therapy

In recent years,the incidence of cancer is increasing rapidly.It is crucial to develop efficient cancer treatment methods and improve the cure rate of patients.At present,there are some cancer treatment methods.However,clinical data show that these treatment techniques have certain shortcomings: have large trauma,poor specificity and large toxic and side effects,and are prone to recurrence.Therefore,it’s imminent to develop more efficient and accurate cancer treatment methods.Sonodynamic therapy(SDT)has excellent therapeutic effects,and deep penetrating ability and non-invasiveness.However,the hypoxic tumor microenvironment makes them low treatment efficiency and hardly completely eliminate the tumor.Fortunately,photothermal therapy(PTT)has no oxygen dependence,the combination of SDT and PTT to ablate tumors shows great research prospects.Therefore,it is of great significance to construct an “all-inone” theranostic nanoplatform with highly efficient imaging function,reactive oxygen species(ROS)yield and photothermal conversion.Naphthalocyanines and their derivatives have large π-conjugated structures and strong absorption in the near-infrared region,which are widely used as photosensitizers and sonosensitizers.However,the poor water-dispersion stability and short circulation time in vivo of naphthalocyanine single molecule limit their therapeutic applictions.While the nanometerization of naphthalocyanines can enhance their hydrophilicity and improve their phagocytosis enrichment in tumor tissue.Gold nanoparticles are widely used in biomedical applications due to their low toxicity,high chemical stability,easy functionalization and nanoenzyme-like activity.To this end,we use microemulsion-assist phase transfer co-assembly method,using oil-soluble gold nanoparticles and copper naphthalene phthalocyanine(Cu NPc)as the building blocks to construct Cu NPc/Au NPs nanocomposites,which can achieve photoacoustic imaging-mediated photothermal-promoted sonodynamic therapy.Based on this,this paper mainly carried out the following research contents:1.The preparation of Cu NPc/Au NPs composites and performance characterization in vitroCu NPc NPs were prepared by a microemulsion-assist self-assembly method to realize the nanometerization of naphthalocyanine molecules.Adjusting the concentration of emulsifiers achieved the controllable self-assembly of Cu NPc NPs.Then,the Cu NPc/Au NPs nanorod was achieved by introducing the co-assembly of gold nanoparticles and copper naphthalocyanine.The results of characterization measurement confirmed that Cu NPc/Au NPs nanocomposite were successfully prepared with confined morphology and uniform size.Under ultrasonic and 808 nm laser irradiation,Cu NPc/Au NPs exhibit excellent reactive oxygen species generation ability and good photothermal performance and stable photothermal cycling.The photoacoustic imaging results showed that the Cu NPc/Au NPs exhibited concentration-and wavelength-dependent photoacoustic imaging properties,which suggesting that Cu NPc/Au NPs can as a promising alternate of excellent photoacoustic imaging-mediated SDT/PTT nanoplatform for tumor therapy.2.Cu NPc/Au NPs composites for photoacoustic imaging-mediated SDT/PTT combined therapy for tumorsThe Cu NPc/Au NPs composites were modified with cell-penetrating peptides(TAT)to improve their dispersibility and enhance the endocytosis of tumor cells.Under ultrasonic(US),Cu NPc/Au NPs@TAT generated a large amount of reactive oxygen species to induce the tumor cell apoptosis.Cytotoxicity experiments results revealed that the combine of SDT/PTT(light for 9 min,US for 5 min)killed 90.5% of cancer cells.The tumor-specific photoacoustic imaging showed that the tumor enrichment concentration of Cu NPc/Au NPs@TAT reached a plateau at post 6 h,and the tumor area could reach 60.1°C under 808 nm laser irradiation by a near-infrared thermal imaging monitor.Treatment results of tumor-bearing mouse showed that the tumor completely ablated without recurrence after post 14 days of Cu NPc/Au NPs@TAT,showing a significant tumor inhibitory effect.Finally,the results of H&E staining,blood routine and biochemical tests showed that Cu NPc/Au NPs@TAT have excellent biosafety in vivo,and can achieve an excellent photoacoustic imaging-mediated SDT/PTT combination therapy integrated nanoplatform for tumor therapy.