Delivery of miR-34a-5p by Folic Acid-Modified β-Cyclodextrin-Grafted Polyethylenimine Copolymer Nanocarriers to Resist KSHV

Abstract

Kaposi’s sarcoma-associated herpesvirus (KSHV) infection can cause a range of malignancies. The use of microRNA (miRNA) to combat viruses and inhibit tumor development has received increasing attention. However, it is difficult for free miRNA to enter into cells directly and to degrade easily. Therefore, the miRNA therapy alone often fails to achieve the expected effect. The selection of an appropriate delivery system for effective miRNA delivery and anti-KSHV is rarely considered. In this study, a β-cyclodextrin-grafted polyethylenimine (β-CD-PEI) was prepared by the chemical synthesis method, and folic acid was further coupled to a nanocarrier (β-CD-PEI-FA). Gel electrophoresis retardation experiments showed that β-CD-PEI-FA could combine with miR-34a-5p to form a drug-carrying nanocomplex β-CD-PEI-FA/miR-34a-5p, which effectively protected miR-34a-5p from serum and nuclease degradation. The particle size and potential were 203.13 ± 0.41 nm and 27.02 ± 0.72 mV, respectively, which were suitable for endocytosis. The cytotoxicity of the vector to KSHV-positive cells BCBL-1 and SK-RG cells was detected by the CCK-8 assay, which proved that the vector had good biosafety in vitro. Further cell experiments showed that β-CD-PEI-FA/miR-34a-5p not only had the ability to transport miR-34a-5p but also accelerated the G2-phase process of BCBL-1 and SK-RG cells and inhibited the proliferation of KSHV-infected cells. Most importantly, it can significantly reduce the expression levels of KSHV genes ORF26, K8.1A, and LANA. Therefore, the nanocarriers may be a promising antiviral drug delivery system with potential applications in the anti-KSHV therapy.