A Self-Energized Photodynamic Therapy Agent Based on Persistent Luminescence Nanoparticles

Abstract

Photodynamic therapy (PDT), an emerging modality for cancer treatment, faces three major challenges: the limited penetration depth of external light, poor photosensitizer stability, and hypoxia in the tumor microenvironment. Persistent luminescence nanoparticles (PLNPs) show great promise for tumor theranostics; although they can generate modest amounts of reactive oxygen species (ROS), their predominant energy-release pathway remains luminescence. To address this limitation, we developed ZGGC@PPy@MnO₂ composite nanoparticles using Zn₁.₂Ga₁.₆Ge₀.₂O₄:Cr (ZGGC) luminescent nanoparticles as the core. In this architecture, the ZGGC core stores energy after ex vivo excitation, the polypyrrole (PPy) coating enhances ROS generation efficiency by nearly fourfold, and the MnO₂ shell both alleviates tumor hypoxia and suppresses unintended energy release from ZGGC in normal tissues. This strategy eliminates the need for conventional photosensitizers and in situ light irradiation, enabling sustained ROS production for nearly 48 h after a single external activation. After MnO₂ coating, ROS generation was suppressed by ~75% under physiological conditions but recovered to ~90% under a simulated tumor microenvironment. In vivo experiments demonstrated a high tumor inhibition rate of 73.2%. Furthermore, a freeze–thaw-assisted centrifugation approach was introduced during synthesis, markedly improving product recovery and redispersibility. Overall, we present a photosensitizer-free, pre-activatable, and TME-gated persistent PDT nanoplatform that sustains ROS generation for ~48 h after a single excitation while simultaneously alleviating hypoxia and suppressing off-target activation.