TY  - JOUR
AU  - Singh, Smriti
AU  - Drude, Natascha
AU  - Blank, Lena
AU  - Desai, Prachi Bharat
AU  - Königs, Hiltrud
AU  - Rütten, Stephan
AU  - Langen, Karl-Josef
AU  - Möller, Martin
AU  - Mottaghy, Felix M.
AU  - Morgenroth, Agnieszka
TI  - Protease Responsive Nanogels for Transcytosis across the Blood−Brain Barrier and Intracellular Delivery of Radiopharmaceuticals to Brain Tumor Cells
JO  - Advanced healthcare materials
VL  - 10
IS  - 20
SN  - 2192-2659
CY  - Weinheim
PB  - Wiley-VCH
M1  - FZJ-2021-03823
SP  - 2100812 -
PY  - 2021
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - 34490744
UR  - <Go to ISI:>//WOS:000692944100001
DO  - DOI:10.1002/adhm.202100812
UR  - https://juser.fz-juelich.de/record/901790
ER  -