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@ARTICLE{Khalin:278048,
      author       = {Khalin, Igor and Adarsh, Nagappanpillai and Schifferer,
                      Martina and Wehn, Antonia and Boide-Trujillo, Valeria J and
                      Mamrak, Uta and Shrouder, Joshua and Misgeld, Thomas and
                      Filser, Severin and Klymchenko, Andrey S and Plesnila,
                      Nikolaus},
      title        = {{N}anocarrier {D}rug {R}elease and {B}lood-{B}rain
                      {B}arrier {P}enetration at {P}ost-{S}troke {M}icrothrombi
                      {M}onitored by {R}eal-{T}ime {F}örster {R}esonance {E}nergy
                      {T}ransfer.},
      journal      = {ACS nano},
      volume       = {19},
      number       = {15},
      issn         = {1936-0851},
      address      = {Washington, DC},
      publisher    = {Soc.},
      reportid     = {DZNE-2025-00554},
      pages        = {14780 - 14794},
      year         = {2025},
      abstract     = {Nanotechnology holds great promise for improving the
                      delivery of therapeutics to the brain. However, current
                      approaches often operate at the organ or tissue level and
                      are limited by the lack of tools to dynamically monitor
                      cargo delivery in vivo. We have developed highly fluorescent
                      lipid nanodroplets (LNDs) that enable tracking of
                      nanocarrier behavior at the subcellular level while also
                      carrying a Förster resonance energy transfer (FRET)-based
                      drug delivery detection system (FedEcs) capable of
                      monitoring cargo release in vivo. Using two-photon
                      microscopy, we demonstrate that circulating LNDs in naïve
                      mouse brain vasculature exhibit 3D real-time FRET changes,
                      showing size-dependent stability over 2 h in blood
                      circulation. Further, in the Nanostroke model, dynamic
                      intravital two-photon imaging revealed that LNDs accumulated
                      within cerebral postischemic microthrombi, where they
                      released their cargo significantly faster than in normal
                      blood circulation. Furthermore, the blood-brain barrier
                      (BBB) became permeable at the microclot sites thereby
                      allowing accumulated FedEcs-LNDs to cross the BBB and
                      deliver their cargo to the brain parenchyma. This
                      microthrombi-associated translocation was confirmed at the
                      ultrastructural level via volume-correlative light-electron
                      microscopy. Consequently, FedEcs represents an advanced tool
                      to quantitatively study the biodistribution and cargo
                      release of nanocarriers at high resolution in real-time. By
                      enabling us to resolve passive targeting mechanisms
                      poststroke, specifically, accumulation, degradation, and
                      extravasation via poststroke microthrombi, this system could
                      significantly enhance the translational validation of
                      nanocarriers for future treatments of brain diseases.},
      keywords     = {Blood-Brain Barrier: metabolism / Blood-Brain Barrier: drug
                      effects / Animals / Fluorescence Resonance Energy Transfer /
                      Mice / Drug Carriers: chemistry / Stroke: drug therapy /
                      Stroke: metabolism / Drug Liberation / Nanoparticles:
                      chemistry / Lipids: chemistry / Thrombosis: drug therapy /
                      Thrombosis: metabolism / Mice, Inbred C57BL / blood-brain
                      barrier (Other) / correlative light-electron microscopy
                      (Other) / microthrombosis (Other) / nanocarriers (Other) /
                      stroke (Other) / Drug Carriers (NLM Chemicals) / Lipids (NLM
                      Chemicals)},
      cin          = {AG Misgeld / LMF},
      ddc          = {540},
      cid          = {I:(DE-2719)1110000-4 / I:(DE-2719)1040180},
      pnm          = {351 - Brain Function (POF4-351) / 899 - ohne Topic
                      (POF4-899)},
      pid          = {G:(DE-HGF)POF4-351 / G:(DE-HGF)POF4-899},
      experiment   = {EXP:(DE-2719)LMF-20190308},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40180319},
      doi          = {10.1021/acsnano.4c17011},
      url          = {https://pub.dzne.de/record/278048},
}