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@ARTICLE{Peng:303087,
      author       = {W. Peng and T. Zhou and L. Hu and V. Vankann and T.
                      Bohn$^*$ and T. Bopp$^*$ and S. L. Kuan and T. Weil},
      title        = {{A}utonomous {A}ctivation of a {G}ated {C}hemiluminescent
                      {P}hotosensitizer {E}nables {T}argeted {P}hotodynamic
                      {T}herapy in {T}umor {C}ells.},
      journal      = {Journal of the American Chemical Society},
      volume       = {147},
      number       = {31},
      issn         = {0002-7863},
      address      = {Washington, DC},
      publisher    = {ACS Publications},
      reportid     = {DKFZ-2025-01512},
      pages        = {27822-27834},
      year         = {2025},
      note         = {2025 Aug 6;147(31):27822-27834},
      abstract     = {Chemiluminescence-based photodynamic therapy (CLPDT) offers
                      a promising solution to the light penetration limits of
                      traditional PDT. However, it lacks spatiotemporal control.
                      Intracellularly activated, self-luminescent PDT agents via a
                      molecular logic gate switch may address this key limitation.
                      We report the synthesis of the self-activating,
                      chemiluminescent photosensitizer (PS) that enables tumor
                      microenvironment-controlled PDT applications. This system
                      integrates a dioxetane-based (Diox) chemiluminescent
                      scaffold with a ruthenium-based (Ru) PS through an oxidation
                      and pH-sensitive linker to enable an AND-gated activation
                      mechanism. The Diox@Ru conjugate is selectively activated by
                      elevated intracellular reactive oxygen species (ROS),
                      characteristic of aggressive cancer phenotypes arising from
                      altered cell metabolism. Upon exposure to ROS (in this case,
                      hydrogen peroxide), the boronic acid ester protecting group
                      of the dioxetane is cleaved, initiating localized
                      chemiluminescence that directly excites the Ru(II) PS to
                      generate cytotoxic singlet oxygen (1O2). Importantly,
                      Diox@Ru remains inert under physiological conditions
                      (neutral pH, low ROS) as well as in the acidic, ROS-rich
                      extracellular tumor milieu (slightly acidic, high ROS). Its
                      activation is confined to the intracellular space of
                      glycolytic cancer cells with mildly alkaline, ROS-rich
                      cytoplasm; and proceeds autonomously, without the need for
                      external light irradiation. In both two-dimensional (2D)
                      monolayer cultures and three-dimensional (3D) tumor spheroid
                      models, Diox@Ru exhibits robust luminescence and efficient
                      1O2 production, resulting in potent cytotoxic effects. These
                      findings present a versatile platform for autonomous
                      activation of self-luminescent PDT agents and highlight the
                      promise of logic-gated chemiluminescence for spatially
                      controlled therapy in complex biological settings.},
      cin          = {FM01},
      ddc          = {540},
      cid          = {I:(DE-He78)FM01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40696775},
      doi          = {10.1021/jacs.5c06761},
      url          = {https://inrepo02.dkfz.de/record/303087},
}