The Construction Of Multi-modal Cooperation System Under The Multiple Responses

With the rapidly advancing of nanomedicine,nanoparticulate drug delivery systems have opened new paths toward the diagnosis and treatment for a variety of tumours.In particular,the environmentally sensitive nanocarriers that can trigger drug release at the tumor site in response to endogenous stimuli such as pH,redox,and enzyme or exogenous stimuli such as temperature,light,magnetic field,ultrasound intensity,or electric pulses have been developed to enable tumor-specific release and thus improve chemotherapeutic efficacy.Based on the tumor microenvironment,including hypoxic,acidic pH,high glutathione concentration,poor heat resistance and so on,this paper constructed four versatile nanoplatforms for combination therapy of cancer,as follows:1.A photothermal/photodynamic/chemotherapy treatment system（UIO-66/MB@MnO₂/5-Fu@PDA）under the dual response of glutathione（GSH）and acid was prepared via hydrothermal reaction.Excited by visible light,MnO₂ and H₂O₂ achieved self-production of oxygen,which converted the oxygen to singlet oxygen by photosensitizer of methylene blue（MB）in this system.In addition,the effective degradation of MnO₂ nanolayers promoted the release of drug 5-fluorouracil（5-Fu）.Under the trigger of 980 nm laser（NIR）,polydopamine（PDA）showed good photothermal conversion ability,which could ablate cancer cells thermally.It was proved that the system had obvious pH/GSH stimulation response to drug release through the sustained release experiment.The final cell experiment also demonstrated that the nanocomposite had a significant interference effect on the growth of Hella cells.2.The chapter coated CuS with gold core was constructed for the first time,then synthesized the Au@CuS@PDA/MB/GOD nanosystem via layer-by-layer self-assembled approach,which achieved photothermal/photodynamic/starvation treatment.Au and CuS were used as photothermal agents,MB as photosensitizer to produce photodynamic effect,and glucose oxidase（GOD）as nutrient blocker to"starve"cancer cells from the source.With the stimulation of NIR,the nanomaterials enriched in the lesion tissues through the EPR effect would generate heat and inhibite of tumor growth.The cell experiments proved that nanomaterials had low biological toxicity and could inhibit the activity of Hela cells maximally through synergistic effects under laser irradiation.3.Hollow CuS nanoparticles were synthesized using Na₂S as the sulfur source and CuCl₂ as the copper source,which could be used not only as photothermal agent,but also as drug carrier.By loading 5-Fu,the CuS@PEI/5-Fu@PDA/GOD nanosystem integrating photothermal/chemotherapy/starvation treatment was synthesized.GOD deprived tumor cells of nutrition,such as oxygen and glucose for starvation therapy.Upon NIR laser triggering,the nanoparticles performed energy conversion rapidly and induced cell apoptosis via hyperthermia,which showed tremendous potential for tumor photothermal therapeutic.The final cytotoxicity experiments demonstrated the nanosystem was biocompatible,and the synergistic effect on tumour treatment was better than of single chemotherapy or starvation therapy.4.The drug carrier of virus-like mesoporous silica（mSiO₂）nanoparticles was obtained via a novel epitaxial growth approach firstly and CuS quantum dots were successfully connected on the surface of mSiO₂ by electrostatic interactions.5-Fu was loaded and used PDA as the"gatekeeper"to form the NIR-induced mSiO₂-CuS/5-Fu@PDA system for photothermal/chemotherapy dual mode treatments.PDA was highly sensitive to pH,leading 5-Fu released specifically,which reduced damage to normal tissue cells.Moreover,the nanosystem had good photothermal stability under NIR illumination.Meanwhile,MTS experiments demonstrated the good biocompatibility of the nanosystem,and tumour growth on the viability of Hela cells via synergistic therapy was better than the single therapy.