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000901790 005__ 20211025171505.0
000901790 0247_ $$2doi$$a10.1002/adhm.202100812
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000901790 037__ $$aFZJ-2021-03823
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000901790 1001_ $$0P:(DE-HGF)0$$aSingh, Smriti$$b0$$eCorresponding author
000901790 245__ $$aProtease Responsive Nanogels for Transcytosis across the Blood−Brain Barrier and Intracellular Delivery of Radiopharmaceuticals to Brain Tumor Cells
000901790 260__ $$aWeinheim$$bWiley-VCH$$c2021
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000901790 520__ $$aDespite 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.
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000901790 7001_ $$0P:(DE-HGF)0$$aDrude, Natascha$$b1
000901790 7001_ $$0P:(DE-Juel1)177838$$aBlank, Lena$$b2
000901790 7001_ $$0P:(DE-HGF)0$$aDesai, Prachi Bharat$$b3
000901790 7001_ $$0P:(DE-HGF)0$$aKönigs, Hiltrud$$b4
000901790 7001_ $$0P:(DE-HGF)0$$aRütten, Stephan$$b5
000901790 7001_ $$0P:(DE-Juel1)131777$$aLangen, Karl-Josef$$b6
000901790 7001_ $$0P:(DE-HGF)0$$aMöller, Martin$$b7
000901790 7001_ $$0P:(DE-Juel1)132318$$aMottaghy, Felix M.$$b8
000901790 7001_ $$0P:(DE-HGF)0$$aMorgenroth, Agnieszka$$b9$$eCorresponding author
000901790 773__ $$0PERI:(DE-600)2645585-7$$a10.1002/adhm.202100812$$gp. 2100812 -$$n20$$p2100812 -$$tAdvanced healthcare materials$$v10$$x2192-2659$$y-
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000901790 9141_ $$y2021
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