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

ABSTRACT: 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 ? peptide nucleic acids (?PNAs) that possess vastly superior RNA-binding affinity, improved solubility, and favorable biocompatibility. For cellular delivery, we encapsulated the ?PNAs in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). Our results show that ?PNAs 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 ?PNA-treated tumors compared to controls. Overall, our work provides a chemical framework for a novel anti-miR therapeutic approach using ?PNAs that should facilitate rational design of agents to potently inhibit oncogenic microRNAs.

SUBMITTER: Gupta A 

PROVIDER: S-EPMC5633812 | biostudies-other | 2017 Dec

REPOSITORIES: biostudies-other