Targeted Peptide Nanofiber-Loaded Stomatocytes for Combined Photodynamic and Photothermal Therapy

Nanotechnology-based photodynamic (PDT) and photothermal (PTT) therapies offer precise treatment by generating reactive oxygen species (ROS) and localized hyperthermia. However, photosensitizer nanodrugs suffer from rapid degradation and limited tumor targeting. To overcome these challenges, we have developed a dual-nanoparticle drug delivery platform based on bowl-shaped polymer vesicles, which were loaded in the protective nanocavity with nanofibers composed of a histidine dipeptide-photosensitizer conjugate. The stomatocytes were surface modified with mannose glycopolymers to induce targeting capacity. This dual nanoparticle platform exhibited enhanced tumor imaging, improved targeting, and increased cellular uptake in tumor cells and 3D tumor spheroids. Under 660 nm laser irradiation, it demonstrated excellent PTT and PDT performance, with significant ROS generation and temperature elevation. This advanced nanomedicine platform, therefore, offers a promising approach for precision cancer therapy.