Design And Preparation Of Two Kinds Of MOFs Structure Nanofunctional Carriers For Cancer Diagnosis And Therapy

Cancer remains one of the deadliest diseases and causes millions of deaths every year.Due to the high mutation rate and genetic heterogeneity of the virus,cancer treatments with high efficiency and low side effects are still being developed,and this has always been a hotspot,a focus and a difficult point in the field of medical research.At present,inorganic-organic composite materials not only have the characteristics of economic security and environmental friendliness of inorganic materials,but also possesse the bio-safety performance of organic materials.Among the numerous therapeutic mechanisms,light-induced therapy has been considered as a non-invasive,direct and accurate platform for cancer treatment,and thus it has attracted much attention.In order to further increase treatment efficiency,avoid excessive use of single components,the adverse side effects of the therapy,such as overheating of photothermal therapy?PTT?,multidrug resistance of chemotherapy and photodynamic therapy?PDT?resistance in low oxygen conditions,the development of synergistic therapies is very important.Through the construction of composite materials and design of integration mechanisms,the synergy effect of different components in biological applications is utilized to effectively improve the anti-cancer performance of the diagnosis and treatment platform.The purpose of this paper are the design and synthesize of multimodal efficient diagnostic and treatment platforms based on inorganic and organic composites,and to study their biological performance as a diagnostic and therapeutic reagent.The studying contents of this paper are summarized as follows:Fe₃O₄/ZIF-8-Au₂₅ nanocomposite was designed and synthesized based on ZIF-8 ZIF-8metal-organic frameworks?MOFs?through green and economical experimental methods.When irradiated with NIR light,the encapsulated Fe₃O₄ nanocrystals not only generate heat to effectively kill tumor cells,but also have the ability of target and MRI image.More importantly,the attached ultra-small Au₂₅?Capt?^-₁₈ cluster?approximately 2.5 nm?not only be severed as photosensitizer,but is also can be directly sensitized under NIR light to cause photodynamic therapy effects.At the same time,the Au₂₅?Capt?^-₁₈ cluster also gives a high thermal effect as a photothermal enhancer.The nano-platform has higher biocompatibility and synergistic therapeutic effects than any single therapy.Meanwhile,compared with the previous chapter,the excitation light source is optimized and improved.The treatment system activated by a single laser can reduce the complexity of the treatment,make the treatment and operation process simple and easy,and have no worry about the combined and separation mode of excitation light.It will results in less phototoxicity and enhanced safety due to the short treatment time.A novel hybrid system by integrating dual-model photodynamic therapies?dual-PDT?in one system was reported.Firstly,we attached core-shell structured up-conversion nanoparticles?UCNPs,NaGdF4:Yb,Tm@NaGdF4?on graphitic-phase carbon nitride?g-C3N4?nanosheets?one photosensitizer?.Then,the as-fabricated nanocomposite and carbon dots?another photosensitizer?were assembled in ZIF-8 metal-organic frameworks through an in situ growth process,realizing the dual-photosensitizer hybrid system employed for PDT via stepwise water splitting.In this system,the UCNPs can convert deep-penetration and low-energy NIR light to higher-energy ultraviolet visible?UV-vis?emission,which matches well with the absorption range of the photosensitizers for reactive oxygen species generation without sacrificing its efficacy under ZIF-8 shell protection.Furthermore,the UV light emitted from UCNPs allows successive activation of g-C₃N₄ and carbon dots,and the visible light from carbon dots upon UV light excitation once again activate g-C3N4 to produce reactive oxygen species,which keeps the principle of energy conservation thus achieving maximize use of the light.A theranostic nanoplatform based on uniformity UCNPs@MIL-100?Fe?NPs was designed and synthesized using one-pot liquid-solid-solution?LSS?method for imaging-guided drug delivery,tumor microenvironment-triggered drug release,and mildly NIR photon-triggered therapy process,so as to achieve tumor microenvironment-enhanced combination therapy under the guidance of multimodal imaging.On the one hand,UCNPs@MIL-100?Fe?NPs convert H2O2 to a large number of reactive oxygen species from the Fenton reaction at 808 nm laser irradiation.On the other hand,the newly developed UCNPs@MIL-100?Fe?NPs also effectively improve the conversion of laser energy into heat under laser irradiation.Therefore,a MIL-100?Fe?layer can be achieved the mechanism of bifunctional synergistic treatment.In addition,the DOX loading UCNPs@MIL-100?Fe?NPs greatly suppress the tumor cell growth in vivo and in vitro under mildly 808nm irradiation for multimode imaging guided the synergic effect of chemo-therapy,PTT and PDT.Importantly,the Gd³⁺/Yb³⁺/Fe³⁺co-doped UCNPs endow the nanomedicine CT/UCL/dual-MRI tri-modal imaging functions,and a mild 808 nm laser is designated as excitation light which avoids overheating effect and low penetration depth.A novel theranostic nanoplatform based on photosensitizer Chlorin e6?Ce6?,photothermal agent carbon dots?CDs?,and imaging agent Gd?III?ions functionalized mesoporous silica hybrid nanospheres has been rationally designed and fabricated.A thermo/pH-coupling sensitive polymer?P?NIPAm-co-MAA??acted as a key“gatekeeper”to control the drug release in the appropriate time and location has been coated on the composite.Upon near-infrared?NIR?light irradiation,Ce6 can generate cytotoxic reactive oxygen species for PDT and carbon dots can convert the photon energy into heat for PTT.Besides the photothermal function,CDs loaded in the channels of mesoporous silica hybrid spheres can also play a role in the hand of“gatekeeper”-polymer to regulate the drug release.Combined with the thermo/pH-sensitive drug release induced controllable chemotherapy,this platform shows excellent synergistic therapeutic efficacy superior to any single/dual-therapy,which were verified evidently by in vitro and in vivo assay.Considering the cheated Gd?III?induced computed tomography?CT?and magnetic resonance imaging?MRI?properties,this multifunctional platform should be of high potential in imaging-guided therapy.