This can be partially solved by performing additional chemical modifications or by using a nanocarrier for efficient oligonucleotide protection and enhanced uptake. However, therapeutic constructs based on nucleic acids face several challenges, such as low cellular uptake and risk of rapid degradation in biological media due to the activity of nucleases. These characteristics make microRNAs a promising tool for researchers trying to influence metabolic pathways in cells during the formation of pathological conditions. Thus, microRNAs can be considered as multifunctional and flexible modulators for regulating the activity of immunocompetent or tumor cells, as well as their interaction. Our findings evidence the potential of dendrimer-based therapeutic constructions for the anti-tumor stem cell therapy worth further investigation. Furthermore, nanoformulations affected the expression of proteins responsible for interactions between the tumor and its immune microenvironment: surface markers (PD-L1, TIM3, CD47) and IL-10. We have shown dendrimer-microRNA nanoformulations to induce cell death in a controllable manner, with cytotoxic effects being more pronounced in tumor cells than in non-tumor stem cells.
The testing was carried out in a panel of glioblastoma and glioma cell lines, glioblastoma stem-like cells and induced pluripotent stem cells.
Herein, we report a preclinical in vitro validation of antitumor activity of nanoformulations containing antitumor microRNA miR-34a and microRNA-21 synthetic inhibitor and polycationic phosphorus and carbosilane dendrimers. In particular, microRNA-based treatment is a solution, which in turn requires specific carriers for intracellular delivery of functional oligonucleotides. Anti-tumor stem cell therapy calls for a new means of treatment. These features are currently assigned to a self-sustaining population of glioblastoma stem cells. Glioblastoma is a rapidly progressing tumor quite resistant to conventional treatment.
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