BACKGROUND: The immune tolerance of the tumor immune microenvironment (TIME) restricts the response to immune checkpoint inhibitors (ICIs). Targeted activation of dendritic cells (DCs) in the TIME seems to be a scheme for improving the therapeutic effect of ICIs treatment. The purpose of this study was to utilize nanotechnology to reprogram the immunosuppressive tumor immune microenvironment METHODS: In this study, a folic acid (FA)-modified nanoassembly (NA) loaded with low-dose paclitaxel (PTX) (FA-PTX NA), self-assembled by distearoylphosphatidylethanolamine-methoxy polyethylene glycol 2000-folic acid (DSPE-mPEG2000-FA) and PTX, was designed to reprogram the DC function of the TIME to sensitize cells to cancer immunotherapy. The characteristics of FA-PTX NAs were studied, and the cytotoxicity, cellular uptake, and DC stimulation of FA-PTX NAs were evaluated RESULTS: The prepared FA-PTX NAs exhibited a slightly negative surface charge, appropriate size and shape, good drug release profiles, and high drug encapsulation efficiency and blood compatibility. The FA-PTX NAs were effectively uptaken by bone BMDCs, increasing the activation and expression of the costimulatory factor of BMDCs CONCLUSIONS: The NA loaded with low-dose PTX can reprogram the DC function in the TIME and exert a synergistic anticancer effect with ICIs in lung cancer treatment. Increased sensitization to ICI therapy as stimulated by PTX-enhanced NAs has potential applications in lung cancer immunotherapy.