Anti-seed PNAs targeting multiple oncomiRs for brain tumor therapy

Glioblastoma (GBM) is one of the most lethal malignancies with poor survival and high recurrence rates. Here, we aimed to simultaneously target oncomiRs 10b and 21, reported to drive GBM progression and invasiveness. We designed short (8-mer) gamma-modified peptide nucleic acids (s gamma PNAs), targeting the seed region of oncomiRs 10b and 21. We entrapped these anti-miR s gamma PNAs in nanoparticles (NPs) formed from a block copolymer of pol-y(lactic acid) and hyperbranched polyglycerol (PLA-HPG). The surface of the NPs was functionalized with alde-hydes to produce bioadhesive NPs (BNPs) with superior transfection efficiency and tropism for tumor cells. When combined with temozolomide, s gamma PNA BNPs administered via convection-enhanced delivery (CED) mark-edly increased the survival (>120 days) of two orthotopic (intracranial) mouse models of GBM. Hence, we estab-lished that BNPs loaded with anti-seed s gamma PNAs targeting multiple oncomiRs are a promising approach to improve the treatment of GBM, with a potential to personalize treatment based on tumor-specific oncomiRs.

Automated summary

In this study, we developed functionalized nanoparticles loaded with anti-seed s gamma PNAs to target oncomiRs 10b and 21 in tumor cells. Combined with temozolomide, these nanoparticles significantly improved the survival of orthotopic mouse models of GBM. This study provides a promising approach to personalized treatment of GBM based on tumor-specific oncomiRs.