Multifunctional polyplex micelles for efficient microRNA delivery and accelerated osteogenesis.

ABSTRACT: MicroRNAs (miRNAs) are emerging as a novel class of molecular targets and therapeutics to control gene expression for tissue repair and regeneration. However, a safe and effective transfection of miRNAs to cells has been a major barrier to their applications. In this work, a multifunctional polyplex micelle named PPP-RGI was developed as a non-viral gene vector for the efficient transfection of miR-218 (an osteogenic miRNA regulator) to bone marrow-derived mesenchymal stem cells (BMSCs) for accelerated osteogenic differentiation. PPP-RGI was designed and synthesized via conjugation of a multifunctional R₉-G₄-IKVAVW (RGI) peptide onto an amphiphilic poly(lactide-co-glycolide)-g-polyethylenimine-b-polyethylene glycol (PPP) copolymer. PPP-RGI self-assembled into polyplex micelles and strongly condensed miR-218 to prevent its RNase degradation. When the PPP-RGI/miR-218 complex was brought into contact with BMSCs, it exhibited high internalization efficiency and a fast escape from endo/lysosomes of the BMSCs. Subsequently, miR-218 released from the PPP-RGI/miR-218 complex regulated gene expressions and significantly enhanced the osteogenic differentiation of BMSCs. The multifunctional peptide conjugated nanocarrier serves as an effective miRNA delivery vector to promote osteogenesis.

SUBMITTER: Li Q 

PROVIDER: S-EPMC10041663 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature