Knauer, Nadezhda ORCID: 0000-0002-5877-3909, Arkhipova, Valeria, Li, Guanzhang, Hewera, Michael ORCID: 0000-0002-4918-2875, Pashkina, Ekaterina ORCID: 0000-0002-4912-5512, Nguyen, Phuong-Hien, Meschaninova, Maria, Kozlov, Vladimir, Zhang, Wei, Croner, Roland S., Caminade, Anne-Marie, Majoral, Jean-Pierre, Apartsin, Evgeny K. and Kahlert, Ulf D. (2022). In Vitro Validation of the Therapeutic Potential of Dendrimer-Based Nanoformulations against Tumor Stem Cells. Int. J. Mol. Sci., 23 (10). BASEL: MDPI. ISSN 1422-0067

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Abstract

Tumor cells with stem cell properties are considered to play major roles in promoting the development and malignant behavior of aggressive cancers. Therapeutic strategies that efficiently eradicate such tumor stem cells are of highest clinical need. Herein, we performed the validation of the polycationic phosphorus dendrimer-based approach for small interfering RNAs delivery in in vitro stem-like cells as models. As a therapeutic target, we chose Lyn, a member of the Src family kinases as an example of a prominent enzyme class widely discussed as a potent anti-cancer intervention point. Our selection is guided by our discovery that Lyn mRNA expression level in glioma, a class of brain tumors, possesses significant negative clinical predictive value, promoting its potential as a therapeutic target for future molecular-targeted treatments. We then showed that anti-Lyn siRNA, delivered into Lyn-expressing glioma cell model reduces the cell viability, a fact that was not observed in a cell model that lacks Lyn-expression. Furthermore, we have found that the dendrimer itself influences various parameters of the cells such as the expression of surface markers PD-L1, TIM-3 and CD47, targets for immune recognition and other biological processes suggested to be regulating glioblastoma cell invasion. Our findings prove the potential of dendrimer-based platforms for therapeutic applications, which might help to eradicate the population of cancer cells with augmented chemotherapy resistance. Moreover, the results further promote our functional stem cell technology as suitable component in early stage drug development.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Knauer, NadezhdaUNSPECIFIEDorcid.org/0000-0002-5877-3909UNSPECIFIED
Arkhipova, ValeriaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Li, GuanzhangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hewera, MichaelUNSPECIFIEDorcid.org/0000-0002-4918-2875UNSPECIFIED
Pashkina, EkaterinaUNSPECIFIEDorcid.org/0000-0002-4912-5512UNSPECIFIED
Nguyen, Phuong-HienUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meschaninova, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kozlov, VladimirUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhang, WeiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Croner, Roland S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Caminade, Anne-MarieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Majoral, Jean-PierreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Apartsin, Evgeny K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kahlert, Ulf D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-692107
DOI: 10.3390/ijms23105691
Journal or Publication Title: Int. J. Mol. Sci.
Volume: 23
Number: 10
Date: 2022
Publisher: MDPI
Place of Publication: BASEL
ISSN: 1422-0067
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ANTICANCER SIRNA COCKTAILS; SHORT INTERFERING RNA; PHOSPHORUS DENDRIMERS; LYN KINASE; DASATINIB; APOPTOSIS; TOOLMultiple languages
Biochemistry & Molecular Biology; Chemistry, MultidisciplinaryMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69210

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