| Cancer is a major problem facing the world today.Conventional chemotherapy has poor specificity and high clearance in the body,which leads to low therapeutic effects with some side effects.How to improve the utilization of drugs and reduce the side effects has become the focus of research.The emergence of nanomedicine brings hope to solve this problem.Among them,the stimulus-responsive nanomedicine system can reduce leakage of drug and increase biosafety.Noble metal nanomaterials have attracted much attention due to their outstanding optical properties and their ability to achieve photo-responsive activation.In this work,three drug delivery systems based on noble metal nanomaterials were prepared,and their stimulus-responsive activation capabilities and anti-tumor mechanisms were explored:(1)After modifying a layer of chitosan on the surface of doxorubicin liposomes,branched gold nanoshells(DOX-lips@BGNS)were prepared by a one-step reduction method in the without seed growth process.Based on the local surface plasmon resonance effect of,the gold nanoshells achieved photothermal conversion,which enabled DOXlips@BGNS to be used for photothermal therapy.The modification of chitosan gave DOXlips@BGNS acidic p H responsiveness.In an acidic environment,the drug release of nanomedicine was triggered by near-infrared laser irradiation.At the same time,the combined effect of chemotherapy and photothermal therapy was completed.In this process,the gold nanoshell decomposed into dispersed gold nanoparticles,which helped further biodegradation.Afterwards,the excellent antitumor effect of DOX-lips@BGNS was confirmed through cell experiments and animal experiments.(2)Silver nanospheres were prepared by the biological template method.Then silverpalladium alloy nanospheres were formed by replacing and reducting on the surface of the silver nanospheres.Finally,a layer of bovine serum albumin was modified on the surface of the silver-palladium alloy nanospheres to load doxorubicin(AgPd@BSA/DOX).The peroxidase-like catalytic activity of the silver-palladium alloy nanospheres was verified by chromogenic experiment of TMB,which can catalyze hydrogen peroxide to produce hydroxyl radicals to kill tumors.The photothermal conversion was achieved by the resonance coupling between the alloy bimetals,which gived the AgPd@BSA/DOX photothermal treatment effect.The acidic p H caused the protonation of doxorubicin to trigger drug release.In an acidic environment,near-infrared laser irradiation can achieve drug burst release from nanocarriers.The detection of reactive oxygen species in cells showed that nanomedicine can catalyze the production of hydroxyl radicals to kill tumors.Cell experiments and animal experiments confirmed that AgPd@BSA/DOX has excellent anti-tumor effects.(3)Considering the excellent catalytic performance of platinum nanomaterials,platinum dendrites were further reduced and grown on the surface of silver nanocubes prepared by the biological template method,and bovine serum albumin was modified on the surface of silver-platinum alloy nanocubes to co-load chlorin e6 and doxorubicin(AgPt@BSA/Ce6/DOX).The catalase-like and peroxide-like catalytic activities of the silver-platinum nanozymes were verified through experiments,and the changes in catalytic activity at different p Hs were explored.The resonance coupling between the alloy bimetals also maked AgPt@BSA/Ce6/DOX have photothermal treatment effects.Drug release experiments also confirmed that the burst release of drugs can be achieved by near-infrared laser irradiation at acidic p H.In vitro detection of reactive oxygen species showed that nanomedicine could produce two kinds of reactive oxygen species for killing tumors and could enhance the photodynamic therapy effect by catalyzing hydrogen peroxide to generate oxygen in a hypoxic environment.Afterwards,cell experiments and animal experiments verified that AgPt@BSA/Ce6/DOX has excellent anti-tumor effects. |
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