Amplifying“eat me signal”during tumor immunogenic cell death(ICD)cascade is crucial for tumor immunotherapy.Inspired by the indispensable role of adenosine triphosphate(ATP,a necessary“eat me signal”for ICD),a ver...Amplifying“eat me signal”during tumor immunogenic cell death(ICD)cascade is crucial for tumor immunotherapy.Inspired by the indispensable role of adenosine triphosphate(ATP,a necessary“eat me signal”for ICD),a versatile ICD amplifier was developed for chemotherapy-sensitized immunotherapy.Doxorubicin(DOX),ATP and ferrous ions(Fe^(2+))were co-assembled into nanosized amplifier(ADO-Fe)throughπ‒πstacking and coordination effect.Meanwhile,phenylboric acid-polyethylene glycol-phenylboric acid(PBA-PEG-PBA)was modified on the surface of ADO-Fe(denoted as PADO-Fe)by the virtue of d-ribose unit of ATP.PADO-Fe could display active targetability against tumor cells via sialic acid/PBA interaction.In acidic microenvironment,PBA-PEG-PBA would dissociate from amplifier.Moreover,high H_(2)O_(2)concentration would induce hydroxyl radical(·OH)and oxygen(O_(2))generation through Fenton reaction by Fe^(2+).DOX and ATP would be released from the amplifier,which could induce ICD effect and“ICD adjuvant”to amplify this process.Together with programmed death ligands 1(PD-L1)checkpoint blockade immunotherapy,PADO-Fe could not only activate immune response against primary tumor,but also strong abscopal effect against distant tumor.Our simple and multifunctional ICD amplifier opens a new window for enhancing ICD effect and immune checkpoint blockade therapy.展开更多
基金the financial support of Natural Science Foundation of China (Nos. 82104108, 82073797, 81874305 and 81773668)China Postdoctoral Science Foundation (2021M693869)Liaoning Natural Science Foundation for Planned Project (2021JH6/10500161, China)
文摘Amplifying“eat me signal”during tumor immunogenic cell death(ICD)cascade is crucial for tumor immunotherapy.Inspired by the indispensable role of adenosine triphosphate(ATP,a necessary“eat me signal”for ICD),a versatile ICD amplifier was developed for chemotherapy-sensitized immunotherapy.Doxorubicin(DOX),ATP and ferrous ions(Fe^(2+))were co-assembled into nanosized amplifier(ADO-Fe)throughπ‒πstacking and coordination effect.Meanwhile,phenylboric acid-polyethylene glycol-phenylboric acid(PBA-PEG-PBA)was modified on the surface of ADO-Fe(denoted as PADO-Fe)by the virtue of d-ribose unit of ATP.PADO-Fe could display active targetability against tumor cells via sialic acid/PBA interaction.In acidic microenvironment,PBA-PEG-PBA would dissociate from amplifier.Moreover,high H_(2)O_(2)concentration would induce hydroxyl radical(·OH)and oxygen(O_(2))generation through Fenton reaction by Fe^(2+).DOX and ATP would be released from the amplifier,which could induce ICD effect and“ICD adjuvant”to amplify this process.Together with programmed death ligands 1(PD-L1)checkpoint blockade immunotherapy,PADO-Fe could not only activate immune response against primary tumor,but also strong abscopal effect against distant tumor.Our simple and multifunctional ICD amplifier opens a new window for enhancing ICD effect and immune checkpoint blockade therapy.
