“Ice and Fire” Supramolecular Cell‐Conjugation Drug Delivery Platform for Deep Tumor Ablation and Boosted Antitumor Immunity

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