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

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. Ice cell & fire nanomedicine supramolecular cell conjugates are reported for combined photothermal/gas therapy/immunotherapy, allowing deep tumor tissue ablation and stimulation of immunity to suppress distant tumor and lung metastasis after only one treatment in vivo.image

Automated summary

A novel photothermal reagent was developed for efficient tumor thermal ablation. Co-loaded with nitric oxide, this reagent anchored to cancer cells through supramolecular assembly, effectively inhibiting distant tumors and lung metastases after only one treatment, while enhancing immune responses.