Anti-tumor Activity of miniPEG-γ-Modified PNAs to Inhibit MicroRNA-210 for Cancer Therapy

• Main Authors: Anisha Gupta (Author), Elias Quijano (Author), Yanfeng Liu (Author), Raman Bahal (Author), Susan E. Scanlon (Author), Eric Song (Author), Wei-Che Hsieh (Author), Demetrios E. Braddock (Author), Danith H. Ly (Author), W. Mark Saltzman (Author), Peter M. Glazer (Author)
• Format: Book
• Published: Elsevier, 2017-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

MicroRNAs (miRs) are frequently overexpressed in human cancers. In particular, miR-210 is induced in hypoxic cells and acts to orchestrate the adaptation of tumor cells to hypoxia. Silencing oncogenic miRs such as miR-210 may therefore offer a promising approach to anticancer therapy. We have developed a miR-210 inhibition strategy based on a new class of conformationally preorganized antisense γ peptide nucleic acids (γPNAs) that possess vastly superior RNA-binding affinity, improved solubility, and favorable biocompatibility. For cellular delivery, we encapsulated the γPNAs in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). Our results show that γPNAs targeting miR-210 cause significant delay in growth of a human tumor xenograft in mice compared to conventional PNAs. Further, histopathological analyses show considerable necrosis, fibrosis, and reduced cell proliferation in γPNA-treated tumors compared to controls. Overall, our work provides a chemical framework for a novel anti-miR therapeutic approach using γPNAs that should facilitate rational design of agents to potently inhibit oncogenic microRNAs.

Item Description

2162-2531
10.1016/j.omtn.2017.09.001