An Energy‐Storing DNA‐Based Nanocomplex for Laser‐Free Photodynamic Therapy

Abstract Photodynamic therapy (PDT) is a therapeutic strategy that is dependent on external light irradiation that faces a major challenge in cancer treatment due to the poor tissue‐penetration depths of light irradiation. Herein, a DNA nanocomplex that integrates persistent‐luminescence nanoparticles (PLNPs) is developed, which realizes tumor‐site glutathione‐activated PDT for breast cancer without exogenous laser excitation. The scaffold of the nanocomplex is AS1411‐aptamer‐encoded ultralong single‐stranded DNA chain with two functions: i) providing sufficient intercalation sites for the photosensitizer, and ii) recognizing nucleolin that specifically overexpresses on the surface of cancer cells. The PLNPs in the nanocomplex are energy‐charged to act as a self‐illuminant and coated with a shell of MnO₂ for blocking energy degradation. In response to the overexpressed glutathione in cancer cells, the MnO₂ shell decomposes to provide Mn²⁺ to catalytically produce O₂, which is essential to PDT. Meanwhile, PLNPs are released and act as a self‐illuminant to activate the photosensitizer to convert O₂ into cytotoxic ¹O₂. Significant tumor inhibition effects are demonstrated in breast tumor xenograft models without exogenous laser excitation. It is envisioned that a laser‐excitation‐free PDT strategy enabled by the PLNP–DNA nanocomplex promotes the development of PDT and provides a new local therapeutic approach.