Magnetically Modulating Singlet Oxygen Photogeneration Within Orthogonally Compact Electron Donor–Acceptor Dyads for Enhanced Photodynamic Antitumor Efficiency

ABSTRACT

The magnetic field has emerged as a powerful tool to regulate the spin‐related photochemical reaction pathways, with photodynamic therapy (PDT) serving as an ideal platform to demonstrate the practical value of the magnetic field effect (MFE). However, there are only a few examples of magnetically enhanced singlet oxygen photogeneration for superior therapeutic efficiency in PDT application. Herein, we demonstrated a magnetically enhanced photodynamic therapy (magneto‐PDT) model employing the orthogonally linked electron donor–acceptor dyad ANOMe‐Cy5, leveraging the MFE to manipulate the intersystem crossing pathways under the concurrent regulation of the hyperfine coupling (HFC) and the difference in g‐factors between the electron donor and acceptor moieties (Δg). The singlet oxygen quantum yield (Φ _Δ ) of ANOMe‐Cy5 was modulated by magnetic fields (0–500 mT), reaching a maximum of 15.1% at 150 mT (MFE on Φ _Δ = 34.9%). Magneto‐PDT exhibited superior cytotoxicity against six tumor cell lines, and simultaneously enabled effective disruption of CT26 tumor spheroids. Notably, in vivo experiments further demonstrated that magneto‐PDT exhibited substantially enhanced inhibitory capability against solid tumors relative to PDT treatment alone. This study establishes magnetic fields as a clinically compatible tool to unlock the therapeutic potential of photoinduced electron transfer‐based photosensitizers, providing a robust strategy for advanced PDT development.