Anti-seed PNAs targeting multiple oncomiRs for brain tumor therapy

作者：Yazhe Wang, Shipra Malik, Hee‐Won Suh, Yong Xiao, Yanxiang Deng, Rong Fan, Anita Hüttner, Ranjit S. Bindra, Vijender Singh, W. Mark Saltzman, Raman Bahal · 发表于：Science Advances · 年份：2023 · DOI：10.1126/sciadv.abq7459 · 被引用次数：43 · 研究领域：Advanced biosensing and bioanalysis techniques、RNA Interference and Gene Delivery、MicroRNA in disease regulation

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) γ-modified peptide nucleic acids (sγPNAs), targeting the seed region of oncomiRs 10b and 21. We entrapped these anti-miR sγPNAs in nanoparticles (NPs) formed from a block copolymer of poly(lactic acid) and hyperbranched polyglycerol (PLA-HPG). The surface of the NPs was functionalized with aldehydes to produce bioadhesive NPs (BNPs) with superior transfection efficiency and tropism for tumor cells. When combined with temozolomide, sγPNA BNPs administered via convection-enhanced delivery (CED) markedly increased the survival (>120 days) of two orthotopic (intracranial) mouse models of GBM. Hence, we established that BNPs loaded with anti-seed sγPNAs targeting multiple oncomiRs are a promising approach to improve the treatment of GBM, with a potential to personalize treatment based on tumor-specific oncomiRs.