Self-enhanced photothermal-chemodynamic antibacterial agents for synergistic anti-infective therapy

Cu_(2-x)S nanostructures have been intensively studied as outstanding chemodynamic therapy(CDT)and good photothermal therapy(PTT)antibacterial agents due to their highly efficient Cu(Ⅰ)-initiated Fenton-like catalytic activity and good photothermal conversion property.However,they still suffer from shortage of Cu(Ⅰ)supply in the long-term and comparatively low inherent photothermal conversion efficiency.Herein,we constructed a self-enhanced synergistic PTT/CDT nanoplatform(Cu_(1.94)S@MPN)by coating Cu_(1.94)S nanoparticles with Fe(Ⅲ)/tannic acid based metal-polyphenol networks(MPN).Activated by the acidic bacterial infection microenvironment,Cu_(1.94)S@MPN could be decomposed to continuously release Cu(Ⅱ),Fe(Ⅲ)ions and tannic acid.As the result of tannic acid-involved Cu and Fe redox cycling,Cu(Ⅰ)/Fe(Ⅱ)-rich CDT could be achieved through the highly accelerated catalytic Fenton/Fenton-like reactions.More importantly,experimental results demonstrated that Cu_(1.94)S@MPN exhibited both excellent photothermal antibacterial and photothermal-enhanced CDT properties to eradicate bacteria in vitro and in vivo.Overall,this novel nanotherapeutics has great potential to become a clinic candidate for anti-infective therapy in future.

Gadolinium Neutron Capture Reaction-Induced Nucleodynamic Therapy Potentiates Antitumor Immunity

A nuclear reaction-induced dynamic therapy,denoted as nucleodynamic therapy(NDT),has been invented that triggers immunogenic cell death and successfully treats metastatic tumors due to its unexpected abscopal effect.Gadolinium neutron capture therapy(GdNCT)is binary radiotherapy based on a localized nuclear reaction that produces high-energy radiations(e.g.,Auger electrons,γ-rays,etc.)in cancer cells when^(157Gd)is irradiated with thermal neutrons.Yet,its clinical application has been postponed due to the poor ability of Auger electrons andγ-rays to kill cells.Here,we engineered a^(157Gd)-porphyrin framework that synergizes GdNCT and dynamic therapy to efficiently produce both•OH and immunogenic 1O2 in cancer cells,thereby provoking a strong antitumor immune response.This study unveils the fact and mechanism that NDT heats tumor immunity.Another unexpected finding is that the Auger electron can be the most effective energy-transfer medium for radiation-induced activation of nanomedicines because its nanoscale trajectory perfectlymatches the size of nanomaterials.Inmouse tumormodels,NDT causes nearly complete regression of both primary and distant tumor grafts.Thus,this^(157Gd)-porphyrin framework radioenhancer endows GdNCT with the exotic function of triggering dynamic therapy;its applicationmay expand in clinics as a new radiotherapy modality that utilizes GdNCT to provoke whole-body antitumor immune response for treating metastases,which are responsible for 90%of all cancer deaths.