Metal-Polyphenol Self-Assembled Nanophotothermal Agent for Precise Mitochondrial Targeted Photothermal Therapy

Nanocarriers have been extensively utilized to improve the stability of photothermal agents in vivo, enhance delivery efficiency, and reduce drug side effects. However, challenges, such as the low safety of carrier materials, insufficient loading of therapeutic agents, and complex preparation procedures, still persist. In this study, the photothermal agent IR780 was encapsulated in network TA-Fe³⁺ (TF) which was self-assembled by tannic acid (TA) and Fe³⁺ to synthesize an acid-responsive multifunctional nanophotothermal agent TF@IR780 (TR). In the slightly acidic tumor microenvironment (TME), network shell TF is degraded, and the internal photothermal agent IR780 is exposed. On the one hand, the TF network can improve the solubility and stability of photothermal agent IR780 in vivo and significantly increase the uptake efficiency in tumor cells. On the other hand, Fe³⁺ exhibits magnetic resonance imaging (MRI) functionality, which combined with the fluorescence imaging of IR780 endows TR with multimodal imaging capabilities. In addition, TR is easy to release photosensitizers through acid response in the low pH environment of TME, and achieves precise damage to mitochondria through mitochondrial anchoring and light regulation. This overcomes the drawbacks of traditional tumor treatment methods, such as poor specificity, and demonstrates efficient and controllable antitumor activity.