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 immuno-therapy.Doxorubicin(DOX),ATP and ferrous ions(Fe2+)were co-assembled into nanosized amplifier(ADO-Fe)through π-π stacking and coordination effect.Meanwhile,phenylboric acid-poly ethylene gly-col-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 H2O2 concentration would induce hydroxyl radical(·OH)and oxygen(O2)generation through Fenton reaction by Fe2+.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 multifunc-tional ICD amplifier opens a new window for enhancing ICD effect and immune checkpoint blockade therapy.

Jiulong Zhang;Xiaoyan Sun;Xiufeng Zhao;Chunrong Yang;Menghao Shi;Benzhuo Zhang;Haiyang Hu;Mingxi Qiao;Dawei Chen;Xiuli Zhao

School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China;Department of Oncology,Affiliated Hongqi Hospital of Mudanjiang Medical College,Mudanjiang 157011,China;Department of Pharmacy,Shantou University Medical College,Shantou 515041,China;Department of Neurology,The Second Affiliated Hospital of Mudanjiang Medical College,Mudanjiang 157009,China

药学学报（英文版）

[1]Jiulong Zhang;Xiaoyan Sun;Xiufeng Zhao;Chunrong Yang;Menghao Shi;Benzhuo Zhang;Haiyang Hu;Mingxi Qiao;Dawei Chen;Xiuli Zhao-.Combining immune checkpoint blockade with ATP-based immunogenic cell death amplifier for cancer chemo-immunotherapy)[J].药学学报（英文版）,2022(09):3694-3709

Amplifying,phenylboric,PADO,targetability

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