In Vitro Validation of the Therapeutic Potential of Dendrimer-Based Nanoformulations against Tumor Stem Cells

Nadezhda Knauer, Valeria Arkhipova, Guanzhang Li, Michael Hewera, Ekaterina Pashkina, Phuong Hien Nguyen, Maria Meschaninova, Vladimir Kozlov, Wei Zhang, Roland S. Croner, Anne Marie Caminade, Jean Pierre Majoral, Evgeny K. Apartsin, Ulf D. Kahlert

Результат исследования: Научные публикации в периодических изданияхстатьярецензирование

Аннотация

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.

Язык оригиналаанглийский
Номер статьи5691
ЖурналInternational Journal of Molecular Sciences
Том23
Номер выпуска10
DOI
СостояниеОпубликовано - 1 мая 2022

Предметные области OECD FOS+WOS

  • 2.04 ХИМИЧЕСКИЕ ТЕХНОЛОГИИ
  • 1.04 ХИМИЧЕСКИЕ НАУКИ
  • 1.06 БИОЛОГИЧЕСКИЕ НАУКИ

Fingerprint

Подробные сведения о темах исследования «In Vitro Validation of the Therapeutic Potential of Dendrimer-Based Nanoformulations against Tumor Stem Cells». Вместе они формируют уникальный семантический отпечаток (fingerprint).

Цитировать