Biomimetic nitric oxide nanogenerators for synergistic gas-mild photothermal therapy of large solid tumor

Available online 13 November 2025

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The mild photothermal therapy of solid tumors was still bottlenecked by the uneven temperature distribution in tumor tissue and the autophagy-mediated resistance. Here, we leveraged the ultra-small size (approximately 0.32 nm) and autophagy inhibition property of nitric oxide (NO) to overcome the above shortcomings for enhanced gas-photothermal therapy of large tumors. NO donor was loaded in mesoporous polydopamine and coated with tumor cell membranes for tumor-targeting delivery. The acid-triggered release of NO could strongly inhibit autophagy to block the pro-survival pathway of tumor cells. Besides, as a small-sized gas, it diffused freely into deep regions and precisely killed the deep-seated tumor cells, resulting in approximately 90% tumor inhibition in the late-stage breast tumor model (> 500 mm3). The NO gas therapy shows great potential to complement other therapeutics for the synergistic therapy of large solid tumors.

Graphical abstractA biomimetic NO nanogenerator was prepared to achieve augmented gas-mild photothermal therapy against large solid tumor through autophagy inhibition and deep penetration.