Fig. 1. Schematic illustration of nanoinducers that remodel the immunosuppressive tumour-lymph node microenvironment to mobilize T and NK cells.

a Screening the size and cholesterol mass ratio for LNs accumulation. The pH/MMP2/temperature-sensitive nanoinducers (NGR/IL-15-IR780/1-MT-Lip, NIL-IM-Lip) were prepared with DPPC (temperature sensitive), IR780, 1-MT, DSPE-PEG₂₀₀₀-MMP2-sensitive pep-IL-15 (MMP2 sensitive) and DSPE-Hyd-PEG₅₀₀₀-NGR (pH sensitive). b After accumulation in tumour tissues, the nanoinducers release IL−15 and NGR, which are then taken up by tumour cells. IR780 induces tumour cell apoptosis via hyperpyrexia and enhances the higher expression of IDO1. 1-MT inhibits kynurenine accumulation under photothermal therapy. c Nanoinducers can be targeted to tumour tissues and directed to LNs. (i) Photothermal therapy reduces tumour burden and elicits ICD to enhance the immune response. (ii) The NIL-IM-Lip accumulated in the tumours comobilized CTLs and NK cells by combining the ICD effect, IL-15 and a PD-1 mAb. (iii) 1-MT was further used to inhibit Treg infiltration in tumours to remodel the tumour microenvironment. (iv) Nanoinducers directed to the LNs comobilized CTLs and NK cells. (v) Nanoinducers directed to the LNs remodelled the LNs microenvironment via the inhibition of Tregs. HyD-PEG₅₀₀₀-NGR: Acylhydrazone bond-PEG₅₀₀₀-NGR; PEG₂₀₀₀-MMP2-IL-15: PEG₂₀₀₀-MMP2 sensitive peptide-IL-15; IM-Lip IR780/1-MT-Liposome, Trp tryptophan, Kyn kynurenine.