Photoelectric Therapy Needle-Combined ICG-Cu(II)-AIBI Infinite Coordination Polymer Nanoparticles for Free Radical Spatiotemporal-Matched Photodynamic-Thermodynamic Tumor Synergistic Therapy

To overcome the critical limitations of poor spatiotemporal coordination and inefficient energy delivery in photodynamic-thermodynamic (TDT-PDT) tumor therapy, we propose a free radical spatiotemporal-matching strategy to enhance therapeutic synergy. An optimized photoelectric therapy needle (PTN) and indocyanine green (ICG)-Cu(II)-AIBI infinite coordination polymer nanoparticles (ICP NPs) were rationally engineered to implement this strategy. The PTN enables precise codelivery of laser irradiation and electric current to the tumor core, achieving spatial overlap of photodynamic and electrothermal activation and free radical generation. The ICP NPs exhibit a high dual-drug loading (85.2%) and pH-responsive release, promoting tumor-selective accumulation and activation. This strategy ensures both spatial overlap and temporal alignment of singlet oxygen and alkyl radical production, maximizing oxidative damage. The ICP NPs display a high maximum tolerated dose (352.10 mg kg –1 ), markedly reducing systemic toxicity. In vitro, ICP NPs exhibit potent cytotoxicity against 4T1 cells (IC 50 = 4.14 μg mL –1, combination index = 0.13), indicating strong synergism. In vivo, under low-energy stimulation and without chemotherapy, this strategy achieves complete tumor inhibition, a low recurrence rate (25% at 60 days), and negligible systemic toxicity. This work establishes a precise, low-toxicity paradigm for spatiotemporally matching dynamic therapy with strong translational potential.