Borrow Strength to Exert: Low-Crystallinity Prussian Blue for Reduction Overload Enhanced Photothermal Therapy

The strategy "Borrow strength to exert" in Sun Tzu's Art of War refers to borrowing external forces to withstand the enemy. Inspired by this, applying this thought to cancer treatment can achieve a more efficient therapeutic effect. Therefore, a fulcrum to borrow the force is vital and significant. Compared with normal cells, tumor cells are more sensitive to redox stress owing to their abnormal redox metabolism. Herein, a regulatory protocol based on chloroauric acid (HAuCl₄) is proposed to prepare small-size and low-crystallinity Prussian blue nanoparticles (LcPB NPs). Notably, LcPB NPs possess higher superoxide dismutase (SOD)-like enzyme activity to induce reduction overload and destroy metabolic processes and organelle functions, which leverages the redox status defect in tumors as the fulcrum. Due to the down-regulation of heat shock proteins (HSPs) mediated by redox imbalance, the inherent photothermal therapy (PTT) mode of LcPB NPs effectively inhibits tumor growth and disrupts calcium homeostasis. Additionally, LcPB NPs can improve the anticancer effect by inhibiting symbiotic bacteria. Meanwhile, their magnetic and optical response performance empowers magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) for tumor diagnosis. Therefore, this work executing the strategy "Borrowing strength to exert" by disturbing the redox balance represents a new antineoplastic paradigm.