Core-Shell Nanoparticle-Peptide@Metal-Organic Framework For PH And Enzyme Stepwise-Responsive Imaging In Living Cells

In-situ imaging of enzyme activity in cancer cells is available for the dynamic evaluation of disease stage and progression.Thus improvement of the sensitivity and specificity of biosensing platform and development of precise imaging strategy for cancer-related enzyme activity are of significance in early diagnosis.Traditional"off-on" fluorescence imaging strategy based on single-recognition switch,is limited in controllable response,accurate imaging and low signal-to-noise ratio.Therefore,developing multi-recognition is in urgent need.Recently,metal-organic frameworks(MOFs)have attracted increasing attention due to their flexible properties and versatile functionalities.By incorporating one or more functional nanoparticles(NPs)into MOF shells,nanoparticle@metal-organic-framework(NP@MOF)could be obtained with improved performance.Combined the benefits of both the nanoparticles and the MOFs effectively,NP@MOFs have exhibited various application potentials in catalysis,sensing,drug delivery and biomedical applications.In this work,taking the advantages of NP@MOF as dual-recognition switch,the following work was carried out to achieve highly specific and sensitive stepwise-responsive imaging:Here we develop a core-shell nanoparticle-peptide@metal-organic framework nanostructure as dual-recognition switch for pH and enzyme stepwise-responsive imaging in living cells.To the best of our knowledge,it is the first time to embed a bio-recognition switch into a MOF.The nanoscale ZIF-8 shell and Au-peptide core of nanoprobes have the capacity for the stimulated response to the acidic environment and cathepsin B(CaB)activity,sequentially,establishing a stepwise-response strategy for CaB detection.The mild synthetic route in solution at room temperature is beneficial for remaining the biological activity of substrate peptide.After cellular internalization into cancer cells,the fluorescence of the nanoprobe can be lighted on effectively by CaB in the lysosome.Colocalization imaging results revealed the localized accumulation of the nanoprobes in the lysosome of HeLa cells,which further verified the capability of the nanoprobe for localized fluorescence imaging.Therefore,this work established a universal platform,which not only demonstrates a new example on the NP@MOF nanostructure as dual-recognition element but also provides a facile and precise imaging strategy for elucidating enzyme activity in disease diagnosis.