PMID- 37127284 OWN - NLM STAT- MEDLINE DCOM- 20230511 LR - 20230515 IS - 1944-8252 (Electronic) IS - 1944-8244 (Print) IS - 1944-8244 (Linking) VI - 15 IP - 18 DP - 2023 May 10 TI - Neural Stem Cells as Carriers of Nucleoside-Conjugated Nanogels: A New Approach toward Cell-Mediated Delivery. PG - 21792-21803 LID - 10.1021/acsami.2c23283 [doi] AB - Neural stem cells (NSCs) present attractive natural drug delivery systems (DDSs). Their migratory potential enables crossing of the blood-brain barrier and efficient and selective accumulation near malignant cells. Here, we present the potential of NSCs as DDSs for nucleoside analogue-conjugated nanogels (NGs). Two different approaches were investigated: the intracellular loading and extracellular cell surface decoration with NGs. For both designs, the tumor-specific migratory potentials of NSCs remained unchanged; however, the intracellular loading showed a shorter NG retention. The cell surface decoration protocol yielded a high loading capacity of 100% after 1 h and a prolonged drug retention. A redox-sensitive linker between NGs and the nucleoside analogue 5-ethynyl-2'-deoxycytidine (EdC) allowed a tumor environment-specific drug release and its efficient and preferential incorporation into the DNA of the tumor cells. Interestingly, the tumor-trafficking potentials of NSCs were significantly potentiated by irradiation of tumor cells. In conclusion, this study indicates the potentials of cell surface-decorated NSCs as DDSs for tumor-specific release, cellular uptake, and incorporation of EdC into DNA. FAU - Morgenroth, Agnieszka AU - Morgenroth A AUID- ORCID: 0000-0002-5712-6881 AD - Department of Nuclear Medicine, RWTH Aachen University, 52074 Aachen, Germany. FAU - Baazaoui, Fatima AU - Baazaoui F AD - Department of Nuclear Medicine, RWTH Aachen University, 52074 Aachen, Germany. FAU - Hosseinnejad, Aisa AU - Hosseinnejad A AD - DWI - Leibniz-Institute for Interactive Materials, RWTH Aachen University, 52074 Aachen, Germany. FAU - Schafer, Laura AU - Schafer L AD - Department of Nuclear Medicine, RWTH Aachen University, 52074 Aachen, Germany. FAU - Vogg, Andreas AU - Vogg A AD - Department of Nuclear Medicine, RWTH Aachen University, 52074 Aachen, Germany. FAU - Singh, Smriti AU - Singh S AUID- ORCID: 0000-0002-2164-9912 AD - DWI - Leibniz-Institute for Interactive Materials, RWTH Aachen University, 52074 Aachen, Germany. AD - Max Planck Institute for Medical Research, Heidelberg 69120, Germany. FAU - Mottaghy, Felix M AU - Mottaghy FM AUID- ORCID: 0000-0002-7212-6521 AD - Department of Nuclear Medicine, RWTH Aachen University, 52074 Aachen, Germany. AD - Department of Nuclear Medicine, Maastricht University Medical Centre, 6229 HX Maastricht, Netherlands. LA - eng PT - Journal Article DEP - 20230501 PL - United States TA - ACS Appl Mater Interfaces JT - ACS applied materials & interfaces JID - 101504991 RN - 0 (Nanogels) RN - 0 (Nucleosides) SB - IM MH - Humans MH - Nanogels MH - Nucleosides MH - Drug Delivery Systems MH - *Neoplasms MH - *Neural Stem Cells PMC - PMC10176478 OTO - NOTNLM OT - drug delivery OT - glioblastoma OT - nanogels OT - neural stem cells OT - nucleoside COIS- The authors declare no competing financial interest. EDAT- 2023/05/02 00:42 MHDA- 2023/05/11 06:42 PMCR- 2023/05/12 CRDT- 2023/05/01 19:43 PHST- 2023/05/11 06:42 [medline] PHST- 2023/05/02 00:42 [pubmed] PHST- 2023/05/01 19:43 [entrez] PHST- 2023/05/12 00:00 [pmc-release] AID - 10.1021/acsami.2c23283 [doi] PST - ppublish SO - ACS Appl Mater Interfaces. 2023 May 10;15(18):21792-21803. doi: 10.1021/acsami.2c23283. Epub 2023 May 1.