摘要Various therapeutic modalities have been engineered for lung cancer treatment,but their clinic appli-cation is severely impeded by the poor therapy efficiency and immunosuppressive microenvironment.Herein,we fabricated a library of small molecule redox-labile nanoparticles(NPs)(i.e.,diPTX-2C NPs,diPTX-2S NPs,and diPTX-2Se NPs)by the self-assembly of dimer paclitaxel(PTX)prodrug,and then utilized these NPs with the traditional Chinese medicine(TCM)Qi-Yu-San-Long-Fang(Q)for effective chemoimmunotherapy on Lewis lung carcinoma(LLC)-bearing mice models.Under the high concen-tration of glutathione(GSH)and H2O2,diPTX-2Se NPs could specifically release PTX in cancer cells and exert a higher selectivity and toxicity than normal cells.In LLC tumor-bearing mice,oral administration of Q not only effectively downregulated programmed death ligand-1(PD-L1)expression,but also remodeled the immunosuppressive tumor immune microenvironment via the increase of CD4+T and CD8+T cell proportion and the repolarization of M2 into M1 macrophages in tumor tissues,collectively achieving superior synergistic treatment outcomes in combination with intravenous PTX prodrug NPs.Besides,we found that the combination regimen also demonstrated excellent chemoimmunotherapeutic performances on low-dose small established tumor and high-dose large established tumor models.This study may shed light on the potent utilization of Chinese and Western-integrative strategy for efficient tumor chemoimmunotherapy.