摘要
Interferon-γ(IFN-γ),secreted by activated T cells predominantly,plays a crucial performance in the tumoricidal immune response.Unfortunately,a high level of IFN-γseverely ignites the immunosuppressive response,especially by increasing the expression of immune checkpoint programmed death-ligand 1(PD-L1)and immunoregulatory enzyme indoleamine 2,3-dioxygenase 1(IDO-1).Herein,we have explored a versatile IFN-γ-nano-integrator(aPD-L1-SH@Ce6@NLG919-PEG,simplified as CNDP)to establish a positive anti-tumor feedback loop to amplify the IFN-γ-mediated tumoricidal effect.In this nanointegrator,photosensitizer chlorin e6(Ce6)mediates photodynamic therapy(PDT)to re-shape immunogenicity and activate the adaptive immune response,followed by the secretion of high-level IFN-γto struggle tumor cells.IDO-1 inhibitor(NLG919)afterwards mitigates the immunosuppressive behavior of IFN-γby neutralizing the function of IDO-1.To turn“waste”into wealth,anti-PD-L1(aPD-L1)antibodies are technically integrated into the nano-integrator to propel the precise attack of breast cancer through ascending PD-L1 blockade.Together,this“three musketeers”nano-integrator tumoricidal tactic may give a unique insight into the clinical anti-tumor therapy.
基金
This work was supported by the National Natural Science Foundation of China(NSFC)(Nos.32171318 and 32101069)
the Faculty of Health Sciences,University of Macao,the Start-up Research Grant(SRG)of University of Macao(No.SRG2018-00130-FHS)
the Science and Technology Development Fund,Macao SAR(Nos.0109/2018/A3,0011/2019/AKP,0113/2019/A2,and 0103/2021/A)
Shenzhen Science and Technology Innovation Commission,Shenzhen-Hong Kong-Macao Science and Technology Plan C(No.SGDX20201103093600004)
We appreciate the assistance and support from the Proteomics,Metabolomics and Drug Development Core,Animal Research Core,and Biological Imaging and Stem Cell Core in the Faculty of Health Sciences,University of Macao.
