HDL Nanoparticles Have Wound Healing and Anti‐Inflammatory Properties and Can Topically Deliver miRNAs

Abstract

microRNAs regulate numerous biological processes, making them potential therapeutic agents. Problems with delivery and stability of these molecules have limited their usefulness as treatments. It is demonstrated that synthetic high-density lipoprotein nanoparticles (HDL NPs) topically applied to the intact ocular surface are taken up by epithelial and stromal cells. microRNAs complexed to HDL NPs (miR-HDL NPs) are similarly taken up by cells and tissues and retain biological activity. Topical treatment of diabetic mice with either HDL NPs or miR-HDL NPs significantly improves corneal reepithelialization following wounding compared with controls. Mouse corneas with alkali burn-induced inflammation, topically treated with HDL NPs, display clinical, morphological, and immunological improvement. These results yield a novel HDL NP-based eye drop for patients with compromised wound healing ability (diabetics) and/or corneal inflammatory diseases (e.g., dry eye).

Eph signaling is regulated by miRNA‐210: Implications for corneal epithelial repair

“…Antago‐210 treatment markedly reduced the time of wound closure when compared to controls (Figure 2A), suggesting a negative role of miR‐210 in corneal epithelial migration. Actin protrusion at the leading edge has been a hallmark of migrating cells 42 and Eph/Ephrin signaling has been reported to modulate actin filament 36,43 . In order to determine the migratory capabilities of corneal epithelial cells after antago‐210 treatment, we took a snapshot of migration 3 h after scratch‐wounding of confluent cultures of hTCEpi cells.…”

“…After 16 h exposure to the antagomirs, linear scratch wounds (in triplicate) were created on the confluent monolayers using a 200 μl pipette tip. Wound closure was monitored using Nikon Biostation CT live cell imaging system at 3 h intervals for 24 h as described before 36 . The percentage decrease in the wound gaps were calculated using ImageJ and normalized to the time 0 wounds.…”

“…Cells were stained with Alexa-488-conjugated phalloidin (Invitrogen) as described previously. 36 Cells were stained with 100 nM DAPI in PBS to label nuclei. Images were taken using an epifluorescence Zeiss Axiovision Z1 microscope with an Apotome slide module (Carl Zeiss).…”

“…Wound closure was monitored using Nikon Biostation CT live cell imaging system at 3 h intervals for 24 h as described before. 36 The percentage decrease in the wound gaps were calculated using ImageJ and normalized to the time 0 wounds. In some experiments, cells were pretreated with an EGFR inhibitor, AG1478 (1 µM) for 1 h before applying a scratch wound.…”

Homo Sapiens (Hsa)-microRNA (miR)-6727-5p Contributes to the Impact of High-Density Lipoproteins on Fibroblast Wound Healing In Vitro

“…Apolipoprotein (apo) A-I, the major protein component of HDL, and apoA-I mimetics can also promote arterial healing by reducing oxidative stress [20], and protect against impaired re-endothelialisation due to dysfunctional HDL [21], although it cannot entirely replicate the effect of HDL [22]. HDL also stimulates the proliferation and migration of type II alveolar epithelial cells during inflammation [23], and topical administration of synthetic HDL nanoparticles improves corneal re-epithelialisation in diabetic mice following wounding, and in corneas subjected to alkali-burn induced inflammation [24]; these particles also delivered microRNA (miRNA; miR) sequences to epithelial and stromal cells in an intact ocular surface [24].…”