Stable Cavitation-Mediated Delivery of miR-126 to Endothelial Cells

Abstract

In endothelial cells, microRNA-126 (miR-126) promotes angiogenesis, and modulating the intracellular levels of this gene could suggest a method to treat cardiovascular diseases such as ischemia. Novel ultrasound-stimulated microbubbles offer a means to deliver therapeutic payloads to target cells and sites of disease. The purpose of this study was to investigate the feasibility of gene delivery by stimulating miR-126-decorated microbubbles using gentle acoustic conditions (stable cavitation). A cationic DSTAP microbubble was formulated and characterized to carry 6 µg of a miR-126 payload per 109 microbubbles. Human umbilical vein endothelial cells (HUVECs) were treated at 20–40% duty cycle with miR-126-conjugated microbubbles in a custom ultrasound setup coupled with a passive cavitation detection system. Transfection efficiency was assessed by RT-qPCR, Western blotting, and endothelial tube formation assay, while HUVEC viability was monitored by MTT assay. With increasing duty cycle, the trend observed was an increase in intracellular miR-126 levels, up to a 2.3-fold increase, as well as a decrease in SPRED1 (by 33%) and PIK3R2 (by 46%) expression, two salient miR-126 targets. Under these ultrasound parameters, HUVECs maintained >95% viability after 96 h. The present work describes the delivery of a proangiogenic miR-126 using an ultrasound-responsive cationic microbubble with potential to stimulate therapeutic angiogenesis while minimizing endothelial damage.

CAG peptide functionalized graphene quantum dots-cationic polymer composite gene carriers

“…5 By introducing exogenous therapeutic target genes into target cells, transfected expression of the target genes in target cells induces rapid proliferation of endothelial cells on TEBVs, thus achieving rapid endothelialization of TEBVs and maintaining their longterm patency. 6 To achieve this goal, researchers have been exploring more efficient and safe genes and gene vectors. 7,8 The group's previous study found that the human C2H2-type zinc finger protein gene ZNF580 is involved in the transcriptional regulation of angiogenesis.…”

Cavitation-Enhanced Drug Delivery and Immunotherapy

“…LuTheryn [ 4 ] et al describe the first use of cationic MBs for targeted treatment of biofilms, which are notoriously drug-resistant and typically are negatively charged. Cationic MBs were also used by He et al [ 5 ] to safely deliver angiogenic microRNA with an eye toward treatment of cardiovascular disease. Kerneis et al [ 6 ] demonstrated the safety of sonoporation to facilitate inner ear drug delivery.…”