Functional Nanomaterials-based Endogenous/Exogenous Stimuli-responsive Cancer Synergetic And Catalytic Therapy

Cancer has become a major threat to human health,and the development of nanotechnology has opened up a new path for cancer treatment.A number of specific functional nanomaterials can effectively response to specific exogenous stimuli(external physical stimuli such as light,ultrasound,and magnetic fields)or endogenous external stimuli(intratumoral biochemical signals such as pH,H2O2,and enzymes),which can be used in the cancer therapeutics.Oriented to the application need in nanomedicine,we have designed and constructed functional nanomaterials with high-efficiency and low-toxicity for various biomedical applications such as drug delivery,chemodynamic therapy,photothermal therapy,based on endogenous/exogenous biological stimuli.The key point of designing and constructing endogenous stimuli-responsive nanomaterials is to study the relationship between the endogenous/exogenous stimuli and the functional properties of nanomaterials.Focusing on the controllable design,biomedical application and biological effects of nanomaterials,this thesis presents the following main research topics:1 Biodegradable hollow mesoporous carbon nanomaterials for photothermal/chemotherapy synergistic tumor therapy.Photothermal therapy(PTT)has attracted great attention due to its high efficiency and minimal damage to normal tissues by using light absorbing materials to convert the external laser energy into heat which increases the temperature of the tumor region and induce the tumor cell death.In this work,hollow mesoporous carbon nanomaterials(HMCNs)with photothermal effect were synthesed to effectively load and deliver chemodrugs,achieving synergistic PTT/chemotherapy.In addition,in this work the biodegradability of HMCNs has been investigated in detail,and the results show that the oxidation treatment improves the biodegradability of HMCNs by enhancing their hydrophilicity.2 Nanocatalytic tumor therapy by biomimetic dual inorganic nanozyme-catalyzed cascade reaction.The emerging nanocatalytic tumor therapy such as chemodynamic therapy(CDT)converts less harmful H2O2 into high-toxic hydroxyl radicals(·OH)via the metal ion-mediated catalytic Fenton chemistry,which has motivated extensive research interests due to the high specificity of the nanocatalytic reactions to tumor microenvironment(TME)and minimized side effects.In this work we have constructed an efficient biomimetic dual inorganic nanozyme-based nanoplatform,which triggers cascade catalytic reactions for TME-responsive nanocatalytic tumor therapy based on ultrasmall Au and Fe3O4 nanoparticles(NPs)co-loaded dendritic mesoporous silica NPs(DMSNAu-Fe3O4 NPs).The in-situ grown Au NPs within the large mesopores as the unique GOx-mimic inorganic nanozyme specifically catalyzes β-D-glucose oxidation into gluconic acid and H2O2 under aerobic conditions,while the as produced H2O2 is subsequently catalyzed by Fe3O4 NPs as the peroxidase(POD)-mimic inorganic nanozyme to liberate highly toxic hydroxyl radicals for inducing tumor-cell death by the typical Fenton-based catalytic reaction.3 Self-evolved H2O2 boosts photothermal-promoted tumor-specific nanocatalytic therapy.Traditional CDT suffers substantially from the insufficiency of intratumoral H2O2 level for inducing a satisfactory therapeutic efficacy.In this work,we have constructed a photothermal-promoted Fenton reaction triggered by self-supplied H2O2,based on the constructed two-dimensional(2D)multifunctional therapeutic Nb2C-IO-CaO2 nanoreactors with enhanced therapeutic efficacy and therapeutic biosafety.These Nb2C-IO-CaO2 nanoreactors employ calcium peroxide(CaO2)as a potent H2O2 supplier to sustain the iron oxide(IO)nanoparticles-mediated catalytic Fenton reaction,and to liberate highly toxic ·OH for inducing tumor-cell apoptosis.Meanwhile,the intratumoral ·OH production is further promoted by the photothermal effect of the Nb2C-IO-CaO2 nanoreactors under near infrared irradiation at the second biowindow.Extensive in vitro and in vivo evaluations have demonstrated significantly enhanced reactive oxygen species(ROS)production and outstanding photothermal effect based on these Nb2C-IO-CaO2 nanoreactors,which synergistically lead to the elevated therapeutic efficacy.