Research On Multifunctional Nanomaterials For Tumor Marker Detection And Cancer Therapy

At present,for major diseases such as cancer,the best way is still to diagnose and treat as soon as possible.Therefore,it is of great significance to develop multifunctional nanomaterials for early analysis and detection of tumor markers and cancer treatment.Electrochemiluminescence（ECL）imaging technology integrates the advantages of electrochemistry,chemiluminescence and imaging technology.In recent years,it has been widely used in the analysis and detection of tumor markers,including cell membrane proteins,intracellular inorganic compounds and biomolecules.For cancer treatment,multimodal treatment strategies have become one of the main methods for researchers to treat tumors.Therefore,the development of multifunctional nanomedicines with multiple therapeutic effects is still the key to the field of nanomedicine.In this paper,a multifunctional ECL imaging probe with low triggering potential based on luminol analog L012 was constructed,which is expected to be used for the visual analysis and detection of tumor markers;and a multifunctional single-atom nano-formulation integrating targeting,drug loading and therapy was synthesized for synergistic cancer therapy.The specific work is as follows:（1）Cathodic ECL microscopy of luminol analog L012 for detection of nucleolin on the surface of tumor cell membranesIn this work,cathode ECL microscope of luminol analog L012 was developed which is expected to be used for the visual analysis and detection of nucleolin on the cell membrane surface.Among them,multi-walled carbon nanotubes（MWCNTs）convert H₂O₂ and dissolved O₂ into reactive oxygen species（ROS）at a voltage of about+0.03 V to oxidize the ground state L012 to an excited state,the excited state L012 releases energy in the form of radiation when returning to the ground state to generate the ECL,and the signal is captured by an electron multiplier camera（EMCCD）to realize ECL imaging of single MWCNTs.The surface of MWCNTs can be further modified with the nucleolin aptamer AS1411.After the probe and tumor cells are incubated,AS1411 binds to nucleolin on the membrane surface,which is expected to realize the ECL imaging analysis and detection of nucleolin.The constructed multifunctional ECL microscope can avoid side reactions caused by high potentials and help maintain cell morphology and biomolecular activity and specificity.（2）Single-atom nanozyme combined with chemodynamic therapy and chemotherapy for enhanced cancer therapyHerein,we present a biocompatible and versatile nanoagent consisting of single-atom iron-containing nanoparticles（SAF NPs）,DOX and A549 cell membrane（CM）.The designed porous Iron-based SACs was originally served as a drug-carrying nanoplatform to release DOX selectively in tumor microenvironment（TME）for tumor chemotherapy（CT）due to the high loading capacity（155%）for DOX.Besides,the designed single-atom nanoagent can perform like peroxidase,which effectively triggers in situ tumor-specific Fenton reaction to generate abundant toxic hydroxyl radicals（·OH）selectively for chemodynamic therapy（CDT）.With the combination of CDT and CT,the constructed SAF NPs@DOX@CM nanoagent demonstrate better in vivo therapeutic performance than single-pathway therapy.In the meantime,after modified with CM,SAF NPs@DOX@CM can achieve homologous binding to target tumor tissues and avoid early clearance.This study proposes a versatile single-atom catalyst（SACs）for enhanced cancer therapy by combining the drug-carrying capabilities of SAF NPs with the enzymatic therapy of single-atom iron active sites.