Fluorinated charge-reversible phthalocyanine nanoemulsions for glioma-targeted dual-modal imaging and self-oxygenated phototherapy.

Gliomas are highly aggressive brain tumors with poor prognosis, limited by inadequate targeting, tumor hypoxia, and the restrictive blood-brain barrier (BBB). Here, we present a fluorinated phthalocyanine manganese-based nanoemulsion for dual-modal imaging and effective phototherapy of gliomas. The amphiphilic phthalocyanine, engineered through side-chain modification and Mn2+ chelation, exhibits "turn-on" near-infrared fluorescence (NIRF), sensitive fluorine-19 magnetic resonance imaging (19F MRI), and high phototherapy efficacy. Self-assembly with fluorinated oil and coating with a folic acid-modified charge-reversible polymer produces a nanoemulsion with markedly enhanced imaging sensitivity and phototherapeutic efficacy. In vitro and in vivo studies demonstrate superior tumor targeting, deep penetration, efficient cellular uptake, dual-organelle localization, and induction of both apoptosis and pyroptosis. In orthotopic glioma models, the nanoemulsion crosses the BBB, accumulates in tumors, suppresses tumor growth, and prolongs survival without obvious systemic toxicity. This strategy underscores the promise of integrating photosensitizer engineering with smart nanoemulsion design for targeted, efficient, and imaging-guided cancer therapy.