Engineering naphthalimide-croconaine dyes: Lysosome-targeted theranostics for near-infrared photoacoustic imaging and multimodal chemodynamic/photothermal therapy

Current cancer therapies are limited by insufficient tumor specificity and poor spatiotemporal control over therapeutic agents. These constraints impede synergistic integration of multimodal treatment approaches, compromising therapeutic efficacy while increasing systemic toxicity. Herein, naphthalimide-croconaine derivatives Cro860 and lysosome-targeted Lyso860 were synthesized by dye integration strategy, forming stable Fe^{2 +} -chelated complexes via the N atom of the indole ring and the C-O group of the croconate molecule. To improve biocompatibility, we assembled LysoFNPs using liposomes. Under acidic lysosomal microenvironment (pH 4.5–5.5), the nanoparticles exhibited enhanced near-infrared (NIR) absorption, boosting photoacoustic imaging and photothermal conversion efficiency while enabling controlled Fe²⁺ release. In 4T1 tumor-bearing models, LysoFNPs demonstrated tumor accumulation and activated concurrent photothermal therapy (PTT) and Fe²⁺-mediated chemodynamic therapy (CDT) under 880 nm NIR irradiation. In vivo studies confirmed tumor monitoring via photoacoustic imaging and 73.66 % tumor growth suppression, highlighting their potential as multimodal theranostic agents.