Scheme 1.

Schematic illustration of triplet combination self-delivery photothermal-boosted-NanoBike (BPSP) tandem-augmented anti-PD-L1 mAb plus SF against HCC. a Preparation of BPSP. b BPSP multi-overcoming immune escape by simultaneously reducing ECM inhibiting tumor angiogenesis, and inducing ICD, finally photothermal/chemical/immune killing tumor cells. (1) NIR-II-activated BPSP performs PTT and remodels ECM by depleting collagen I, promoting deep penetration of therapeutics and immune cells. (2) SF released from BPSP by PTT promotion, which exerts anti-vascular effects and down-regulates PD-L1 via RAS/RAF/ERK pathway inhibition, enhancing the efficacy of anti-PD-L1 mAb in overcoming immune escape. (3) The anti-PD-L1 mAb block PD-1/PD L1 recognition and the response rates of anti-PD-L1 mAb was further increased by PTT-induced ICD