Transglutaminase-Polyethyleneimine Nanoflowers Mediated Cellular Delivery of Anti-miR-210 for Effective Glioblastoma Therapy

Glioblastoma (GBM) is a deadly tumor of the central nervous system (CNS) having a dismal prognosis. miRNA-based therapeutics hold immense potential for GBM therapy; however, its delivery remains a daunting challenge. MicroRNA-210 has been established as a critical oncomiR in GBM. Our group has developed novel, PEI-functionalized transglutaminase-based nanoflowers (TGNFs, ∼61 nm in diameter) for the efficient delivery of anti-miR-210 to glioblastoma cells in vitro . TGNFs show low cytotoxicity to normal human fibroblasts, do not affect the liver and kidney health of CD1 mice, and offer >95% anti-miR encapsulation efficiency, serum stability, and protection against polyanion moieties. Their synthesis is cost-effective and does not involve the application of harsh chemicals. TGNFs successfully delivered anti-miR-210 to glioblastoma cells, decreasing cellular proliferation and migration and increasing apoptosis. Overall, this research highlights the potential of TGNFs as delivery agents in miRNA inhibition therapy and encourages further preclinical studies to explore the potential of miR-210 as a therapeutic target in GBM and various other cancers where the oncogenic role of miR-210 has been well-established.