A continuous stimuli-responsive system for NIR-II fluorescence/photoacoustic imaging guided photothermal/gas synergistic therapy

Abstract

Nanosystems responsive to a tumor microenvironment (TME) have recently attracted great attention due to their potential in precision cancer theranostics. However, theranostic nanosystems with a TME-activated consecutive cascade for the accurate diagnosis and treatment of cancer have rarely been exploited. Herein, an activatable theranostic nanosystem (Bi₂S₃-Ag₂S-DATS@BSA-N₃ NYs) is designed and constructed on the basis of a one-pot biomineralization method and surface functional modification to improve second near-infrared (NIR-II) fluorescence/photoacoustic (PA) imaging-guided photothermal therapy (PTT)/gas therapy (GT). Based on enhanced penetration and retention (EPR) effect-mediated tumor accumulation, the tumor-overexpressed glutathione (GSH) can accelerate hydrogen sulfide (H₂S) generation from the nanoparticles by reacting with the encapsulated diallyl trisulfide (DATS). Meanwhile, the in situ released H₂S can be used not only for gas therapy, but also to start the reduction of –N₃(−) to –NH₂(+), thereby enhancing the tumor-specific aggregation of NYs. As a result, the activatable nanosystems with excellent tumor accumulation and biodistribution could achieve an accurate NIR-II/PA dual-modality imaging for guiding the synergistic anticancer efficacy (PTT/GT). Thus, this work provides a promising TME-mediated continuously responsive strategy for efficient anticancer therapy.