Advances in ultrasound-targeted microbubble-mediated gene therapy for liver fibrosis

Abstract

Hepatic fibrosis develops as a wound-healing scar in response to acute and chronic liver inflammation and can lead to cirrhosis in patients with chronic hepatitis B and C. The condition arises due to increased synthesis and reduced degradation of extracellular matrix (ECM) and is a common pathological sequela of chronic liver disease. Excessive deposition of ECM in the liver causes liver dysfunction, ascites, and eventually upper gastrointestinal bleeding as well as a series of complications. However, fibrosis can be reversed before developing into cirrhosis and has thus been the subject of extensive researches particularly at the gene level. Currently, therapeutic genes are imported into the damaged liver to delay or prevent the development of liver fibrosis by regulating the expression of exogenous genes. One technique of gene delivery uses ultrasound targeting of microbubbles combined with therapeutic genes where the time and intensity of the ultrasound can control the release process. Ultrasound irradiation of microbubbles in the vicinity of cells changes the permeability of the cell membrane by its cavitation effect and enhances gene transfection. In this paper, recent progress in the field is reviewed with emphasis on the following aspects: the types of ultrasound microbubbles, the construction of an ultrasound-mediated gene delivery system, the mechanism of ultrasound microbubble–mediated gene transfer and the application of ultrasound microbubbles in the treatment of liver fibrosis.

Multicore Liquid Perfluorocarbon‐Loaded Multimodal Nanoparticles for Stable Ultrasound and 19F MRI Applied to In Vivo Cell Tracking

“…Several modifications of microbubble formulations have been proposed to overcome the stability issues, which mainly focused on shell composition, in order to increase the circulation time and durability of the microbubble agents . Examples of these modifications include the combination of different shell compositions, like albumins, phospholipids, or polymers with different gaseous cores, such as high molecular weight gases, for example, perfluorocarbon (PFC, C 3 F 8 or C 4 F 10 ) or sulfur hexafluoride (SF 6 ) . Nevertheless, none of these attempts resulted in an in vivo stability exceeding 1 h. Additionally, the large size of these agents (typically 2 µm) prevents extravasation and can effectively limit intracellular localization.…”

“…Sub‐micrometer droplets consisting of liquid PFCs are able to extravasate and were proposed as phase‐change agents that can be vaporized with an acoustic trigger and subsequently generate contrast . The droplet‐to‐bubble conversion upon vaporization, comes with a fivefold increase in diameter .…”

ASIC1a inhibits cell pyroptosis induced by acid‐induced activation of rat hepatic stellate cells

“…The occurrence and development of liver fibrosis is a multipath and multifactor participation process. HSCs play an important role in the development of liver fibrosis [24,26]. The main pathological change involves excessive synthesis and abnormal deposition of the ECM.…”

Physical‐, chemical‐, and biological‐responsive nanomedicine for cancer therapy

“…Ultrasound technology has been widely used to microbubble or gas triggered drug delivery (Z. Chen et al, 2018;C. Huang, Zhang, & Bai, 2017;Lv et al, 2017;.…”