“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.