Synthesis And Collaborative Phototherapy Of Nanomaterials Based On Silicon Phthalocyanine

In recent years,people have gradually developed and utilized nanomaterials that are excited by light,heat,magnetism,ultrasound and other"bio-friendly" factors,in order to obtain nanocomposite materials with multiple functions for diagnosis and treatment.Among them,phototherapy includes two types:photothermal therapy(PTT)and photodynamic therapy(PDT).They use light to excite the photothermal material or photosensitizer to generate heat(>50?)or singlet oxygen(1O2)to "burn" or "kill"the tumor inside the cancer cell.Compared with mainstream cancer treatment methods such as surgery,chemotherapy,and radiotherapy,light induction therapy has the advantages of simple operation,non-invasiveness,and less toxic side effects,which makes it attract more and more people's interest in cancer treatment.However,due to the inherent hypoxic environment inside the tumor and the oxygen consumption during PDT treatment,the treatment efficiency of oxygen-dependent PDT is greatly inhibited.The non-oxygen-dependent PTT can generate heat under light irradiation to achieve simultaneous destruction of the tumor,thereby making up for the inhibition of PDT efficiency caused by the lack of oxygen in the tumor environment.Therefore,the synergy of PDT and PTT can greatly improve the therapeutic effect.Thus,the multifunctional nanomedicine with the combined therapeutic effect of PDT and PTT is attracting people's great research interest.However,poor tumor selectivity and low biological stability are still the main challenges to be solved in this field.Due to the abnormal structure of tumor blood vessels,nanomaterials can accumulate at the tumor site by retaining the high permeability and long retention(EPR)effect,thereby having passive targeting of the tumor.However,most nanomedicines are mostly combined through physical superposition,electrostatic attraction and Van der Waals interaction,making them unstable or dissociated in the physiological environment,leading to weakened tumor targeting,reduced therapeutic effects,and enhanced side effects.Therefore,the design and construction of nanomedicine with high biological stability and strong tumor selectivity is the general trend in this field.Moreover,by introducing cancer targeting factors,nanomaterials will be given active targeting functions,thereby obtaining multifunctional nanomaterials with both active/passive dual targeting.Phthalocyanine belongs to the category of second-generation photosensitizers.Among them,silicon phthalocyanine(SiPc)has great potential for PDT application due to its good biocompatibility,high singlet oxygen yield and fluorescence yield.On the other hand,graphene oxide has great advantages in surface modification of photothermal materials due to its abundant functional group structure(carboxyl,hydroxyl,carbonyl,etc.),excellent physical and chemical properties and good biocompatibility.Polypeptides with RGD sequence have high selectivity for the overexpression of ?v?3 integrin on the surface of certain cancer cells and tumor blood vessels.Based on the above background,we used the method of covalent synthesis to connect amino-silicon phthalocyanine and c(RGDyK)with graphene oxide to obtain the composite nano-material RGD-graphene oxide-silicon phthalocyanine(RGD-GO-SiPc).And carry out a series of photophysical and photochemical characterization and PDT/PTT combination therapy biological performance test.The specific experiment content is as follows:1 Covalently combine tumor targeting ligand RGD,photosensitizer silicon phthalocyanine and photothermal material graphene oxide through a coupling reaction to obtain composite nanomaterial RGD-GO-SiPc.The morphological size of the composite material was characterized by atomic force microscopy and DLS,and the size distribution was obtained in the optimal cell uptake area.The infrared,Raman and XPS spectra of the samples were tested,which proved the successful synthesis of covalent bonds.Ultraviolet-visible absorption spectrum and fluorescence spectrum prove that the composite material has strong absorption ability in the near infrared and red fluorescent labeling ability.Detailed tests show that the composite nanomaterial has a high singlet oxygen generation capacity,and its photothermal conversion efficiency under 808 nm laser can reach 25.6%,indicating the feasibility of being used as a photodynamic/photothermal synergistic therapeutic drug.2 The intracellular fluorescence experiment proved that this composite material can actively target cancer cells with high expression of ?v?3 integrin,and perform fluorescence imaging at the same time.Intracellular ROS experiments show that composite materials can generate reactive oxygen species in cancer cells under the irradiation of a light source.The results of cytotoxicity experiments show that the composite material can be combined with photodynamic/photothermal therapy to kill cancer cells,and the combined treatment effect is higher than the single treatment effect.3 The nanomedicine was introduced into tumor-bearing mice through tail vein injection to observe the therapeutic effect.The results of fluorescence imaging in mice show that the composite material can perform fluorescence imaging of tumor sites,indicating its remarkable tumor selectivity.The results show that RGD-GO-SiPc can be used for PDT/PTT synergistic therapy,and has a very obvious inhibitory effect on tumors.The H&E staining results of normal tissues in mice showed that RGD-GO-SiPc would not affect normal tissues.The effect of treatment in mice shows that the composite nanomaterial is a multi-functional anti-cancer drug with great development potential.