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

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 1 O2 . 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.