Microfluidically fabricated self-oxygen-supplied DL-86 lipid nanoplatform for in vitro synergistic photodynamic/photothermal dual phototherapy against hypoxia-tolerant glioblastoma

Glioblastoma (GBM) bears sustained intratumoral hypoxia that blocks oxygen-dependent photodynamic therapy (PDT). Hypoxia suppresses Type II photochemical reactions and singlet oxygen (¹O₂) generation, while oxygen-free photothermal therapy (PTT) can complement PDT for synergistic tumor suppression. Copper phthalocyanine DL-86 is a single NIR dual-responsive photosensitizer capable of simultaneous ROS and heat production, yet its anti-tumor potency is limited by tumor hypoxia and poor cellular uptake. Herein, microfluidics was adopted to fabricate self-oxygenated liposomes DL-86@CAT@Lip co-loaded with DL-86 and catalase (CAT). The uniform spherical nanoparticles (114.7 nm) exhibited excellent colloidal and serum stability. Encapsulated CAT decomposed intracellular H₂O₂ to relieve hypoxia, and the nanosystem achieved a photothermal conversion efficiency of 46.15%. Under 660 nm laser irradiation, combined PDT/PTT drastically reduced hypoxic C6 glioma cell viability to ~20.3%. Hemolysis tests confirmed favorable intravenous hemocompatibility. This work first proves that the self-oxygenation liposomal platform enhances hypoxic anti-GBM dual phototherapy, supplying an in vitro concept and a blueprint for brain tumor phototherapeutic nanomedicines.