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@ARTICLE{Singh:901790,
      author       = {Singh, Smriti and Drude, Natascha and Blank, Lena and
                      Desai, Prachi Bharat and Königs, Hiltrud and Rütten,
                      Stephan and Langen, Karl-Josef and Möller, Martin and
                      Mottaghy, Felix M. and Morgenroth, Agnieszka},
      title        = {{P}rotease {R}esponsive {N}anogels for {T}ranscytosis
                      across the {B}lood−{B}rain {B}arrier and {I}ntracellular
                      {D}elivery of {R}adiopharmaceuticals to {B}rain {T}umor
                      {C}ells},
      journal      = {Advanced healthcare materials},
      volume       = {10},
      number       = {20},
      issn         = {2192-2659},
      address      = {Weinheim},
      publisher    = {Wiley-VCH},
      reportid     = {FZJ-2021-03823},
      pages        = {2100812 -},
      year         = {2021},
      abstract     = {Despite profound advances in treatment approaches, gliomas
                      remain associated with very poor prognoses. The residual
                      cells after incomplete resection often migrate and
                      proliferate giving a seed for highly resistant gliomas. The
                      efficacy of chemotherapeutic drugs is often strongly limited
                      by their poor selectivity and the blood brain barrier (BBB).
                      Therefore, the development of therapeutic carrier systems
                      for efficient transport across the BBB and selective
                      delivery to tumor cells remains one of the most complex
                      problems facing molecular medicine and nano-biotechnology.
                      To address this challenge, a stimuli sensitive nanogel is
                      synthesized using pre-polymer approach for the effective
                      delivery of nano-irradiation. The nanogels are cross-linked
                      via matrix metalloproteinase (MMP-2,9) substrate and armed
                      with Auger electron emitting drug
                      5-[125I]Iodo-4”-thio-2”-deoxyuridine ([125I]ITdU) which
                      after release can be incorporated into the DNA of tumor
                      cells. Functionalization with diphtheria toxin receptor
                      ligand allows nanogel transcytosis across the BBB at tumor
                      site. Functionalized nanogels efficiently and increasingly
                      explore transcytosis via BBB co-cultured with glioblastoma
                      cells. The subsequent nanogel degradation correlates with
                      up-regulated MMP2/9. Released [125I]ITdU follows the
                      thymidine salvage pathway ending in its incorporation into
                      the DNA of tumor cells. With this concept, a highly
                      efficient strategy for intracellular delivery of
                      radiopharmaceuticals across the challenging BBB is
                      presented.},
      cin          = {INM-4 / PTJ-NMT},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-4-20090406 / I:(DE-Juel1)PTJ-NMT-20090406},
      pnm          = {5253 - Neuroimaging (POF4-525)},
      pid          = {G:(DE-HGF)POF4-5253},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {34490744},
      UT           = {WOS:000692944100001},
      doi          = {10.1002/adhm.202100812},
      url          = {https://juser.fz-juelich.de/record/901790},
}