“Ice & Fire” Supramolecular Cell-Conjugation Drug Delivery Platform for Deep Tumor Ablation and Boosted Anti-Tumor Immunity

Cancer recurrence and metastasis are two major challenges in the current clinical therapy. Here, we synthesized a novel diketopyrrolopyrrole-based photothermal reagent (DCN) with unique J-aggregation-induced redshift to achieve efficient tumor thermal ablation under safe power (0.33 W/cm 2 ). Meanwhile, S-nitroso-N-acetylpenicillamine (SNAP) was co-loaded with near-infrared (NIR)-absorbing DCN in amphiphilic polymers to realize heat-induced massive release of nitric oxide (NO), which could form oxidant peroxynitrite (ONOO – ) to active MMPs, thereby degrading the compact tumor extracellular matrix (ECM) to improve the ablation depth and infiltration of immune cells. Through a facile supramolecular assembly method, the DCN/SNAP nanoparticles were anchored to liquid nitrogen-frozen cancer cells (LNF), achieving enhanced anti-tumor immune responses and effective inhibition of distant tumor and pulmonary metastases after only one treatment. The safety and effectiveness of this supramolecular cell-conjugation platform were verified by 2D/3D cellular experiments and bilateral tumor model, confirming the thermal ablation-gas permeation-antigen presentation therapeutic mode had promising anticancer prospects. This article is protected by copyright. All rights reserved