Preparation And Anti-tumor Properties Evaluation In Vitro Of Nanocarriers Based On Chemo-Photothermal/Photodynamic Synergistic Therapy

Cancer,also known as malignant tumor,is one of serious diseases that threat to human life and health.Currently,surgery,radiotherapy and chemotherapy is widely used in clinical cancer therapy,among which chemotherapy is the most important one.However,chemotherapy can cause terrible damage to healthy tissues or organs,so a more effective treatment method with less side effects is urgently needed.Photothermal therapy and photodynamic therapy have become the focus of cancer treatment because of their unique advantages.In fact,a single therapy mode can not treat cancer entirely and effectively,then to create an ideal nanocarrier system,which can combine one or two or more forms of chemotherapy,photothermal therapy,photodynamic therapy to perform the function together is very challenging and significant.Based on this,a series of multifunctional nanocarrier systems were designed in my paper and HeLa and MCF-7 cells were used as cell models to study the effects of chemotherapy,chemo-photothermal synergistic therapy,chemo-photodynamic synergistic therapy,and photothermal-photodynamic synergistic therapy.1)Graphene quantum dots(GQDs)and doxorubicin(DOX)were encapsulated into the cores of PLGA nanoparticles coated with bovine serum albumin to construct pH-responsive nanoparticles(GQDs@DOX/PB)with spherical core-shell structures to achieve bioimaging and effective drug delivery.The results showed that the nanoparticles had the best particle size(200-300 nm).Based on the EPR effect,the nanoparticles could prolong blood circulation and gradually accumulate into tumors.Meanwhile,GQDs@DOX/PB entered the cells and mainly located inside the cytoplasm lysosomes and cytoplasm.In addition,in vitro cytotoxicity measurements showed that the nanoparticles could significantly inhibit HeLa cell proliferation and effectively reduce cells survival rate.2)pH-responsive multifunctional drug delivery system(DOX/PB@Ce6)was prepared by loading anticancer drug DOX and photosensitizer chlorin(Ce6)via a simple method.With optimal size,high synthesis yield,pH-responsive drug release behavior and excellent singlet oxygen production,the DOX/PB@Ce6 have the potential to enhance anti-tumor efficiency.More importantly,the in vitro chemo-photodynamic synergetic experiments indicated that the DOX/PB@Ce6 NPs had remarkable cancer cell killing efficiency under laser irradiation.Notably,by hemolysis assay,the DOX/PB@Ce6 displayed excellent blood compatibility and were expected to be applicable for intravenous injection.3)GQDs or MB together with DOX were encapsulated into the cores of PLGA nanoparticles coated with BSA via a double emulsion-solvent evaporation method to construct pH-responsive nanoparticles(GQDs@DOX/PB and MB@DOX/PB)for chemo-photothermal/photodynamic synergetic therapy.The nanoparticles with high drug loading capacity and pH responsive drug release behavior,which could reach the tumor site due to EPR effect and achieve targeted drug release in acidic environment.In addition,the GQDs@DOX/PB exhibited excellent photothermal property and stability under near 808-nm laser irradiation.Meanwhile,the nanoforplats showed more efficient killing capacity of cancer cells than single therapy,indicating that the nanoforplats have potential for chemo-photothermal/photodynamic synergistic therapy.4)The NGO nanosheets were successfully prepared by a modified Hummers method and then carboxylated to introduce more carboxy groups and obtain carboxylated graphene oxide(NCGO),further enabling us to successfully modify NCGO with targeted folic acid(NCGO-FA).And then the NCGO-FA to separately load the DOX and MB via ?-? stacking and electrostatic attractions,forming NCGO@DOX-FA and NCGO@MB-FA nanoplatforms for targeted drug delivery and photothermal-chemo/photodynamic synergetic therapy.The NCGO-FA nanocomplexes have an ultrahigh polyaromatic surface area,a high load content of drugs,pH and thermal dual-responsive drug release behaviors and excellent photothermal conversion efficiency and photostability.Meanwhile,after loading the nanoplatforms with DOX or MB,NCGO-FA delivered drugs into cancer cells by FA receptors and triggered the drug release by heat and in acidic tumor environments.More importantly,compared with individually applied photothermal therapy,photodynamic therapy,or chemotherapy,the photothermal-chemo/-photodynamic synergistic therapy with the nanoplatform exhibits a remarkable synergistic effect,resulting in a distinguished antitumorefficiency.Notably,this work proposes a facile and versatile method to construct a dual-responsive versatile nanoplatform that combines photothermal-chemo and photodynamic therapies,and these nanoplatforms have excellent application prospects for tumor therapy.