Photoregulated plasmon enhanced controllable hydrogen sulfide delivery for photothermal augmented gas therapy

Gas therapy has emerged as a promising “green” treatment modality for malignant cancer, however, the targeted delivery of gas donors as well as the controlled gas release remain a formidable challenge. Herein, self-assembled gold nanovesicles (GVs) loaded with ammonium sulfide ((NH4)2S) (denoted as GV-(NH4)2S) were developed as theranostic nanoplatform for near-infrared (NIR)-activated in-situ hydrogen sulfide (H2S) generation, controllable gas delivery, and combined photothermal/gas therapy of cancer. GVs had the following features, (1) large hollow cavity, offering high encapsulation efficiency of (NH4)2S (∼95%), (2) strong plasmon coupling effect, promoting high photothermal effect under NIR laser irradiation. Upon laser irradiation, GVs were ruptured, thus allowing the simultaneous release and decomposition of (NH4)2S to generate H2S. The generated H2S induced significant mitochondrial damage and thus reduced adenosine triphosphate (ATP) energy level. Consequently, upon integration, GV-(NH4)2S triggered substantial tumor cell killing in vitro and complete 4T1 tumor ablation in vivo, with negligible tumor recurrence and systemic side effects, under the guidance of photoacoustic (PA)/photothermal duplex imaging. This work highlighted the great promise of GVs as a versatile nanocarrier for spatio-temporally controlled and on-demand delivery of gaseous messengers to achieve precision cancer theranostics.