Acoustically active liposome‐nanobubble complexes for enhanced ultrasonic imaging and ultrasound‐triggered drug delivery

Abstract

Ultrasound is well known as a safe, reliable imaging modality. A historical limitation of ultrasound, however, was its inability to resolve structures at length scales less than nominally 20 µm, which meant that classical ultrasound could not be used in applications such as echocardiography and angiogenesis where one requires the ability to image small blood vessels. The advent of ultrasound contrast agents, or microbubbles, removed this limitation and ushered in a new wave of enhanced ultrasound applications. In recent years, the microbubbles have been designed to achieve yet another application, namely ultrasound-triggered drug delivery. Ultrasound contrast agents are thus tantamount to 'theranostic' vehicles, meaning they can do both therapy (drug delivery) and imaging (diagnostics). The use of ultrasound contrast agents as drug delivery vehicles, however, is perhaps less than ideal when compared to traditional drug delivery vehicles (e.g., polymeric microcapsules and liposomes) which have greater drug carrying capacities. The drawback of the traditional drug delivery vehicles is that they are not naturally acoustically active and cannot be used for imaging. The notion of a theranostic vehicle is sufficiently intriguing that many attempts have been made in recent years to achieve a vehicle that combines the echogenicity of microbubbles with the drug carrying capacity of liposomes. The attempts can be classified into three categories, namely entrapping, tethering, and nesting. Of these, nesting is the newest-and perhaps the most promising.

Enhancement of cancer specific delivery using ultrasound active bio-originated particles

“…While these theranostic agents exhibit multiple attractive properties, namely enhanced bio-availability with prolonged circulation time, preferential tumor accumulation owing to the enhanced permeability and retention (EPR) effect and imaging compatibility with existing detection modalities (e.g., magnetic resonance imaging or optical excitation), their clinical translation remains challenging. 13,14 Moreover, when integrated with super-paramagnetic iron-oxide nanoparticles, the assembly provided dual contrast in both magnetic resonance (MR) and US imaging. [8][9][10] Microbubbles (micro-meter sized bubble, MBs) and liposomes (Lipos) are emerging biocompatible materials for cancer diagnosis and treatment, and therefore represent a safer alternative to conventional theranostic agents.…”

Smart Drug Delivery Strategies Based on Porous Nanostructure Materials

“…In addition, ultrasound-triggered drug delivery vehicles can be combined with ultrasound contrast agents or microbubbles to create "theranostics" that incorporate both diagnostics via imaging and therapy via drug delivery [102]. Ultrasound-activated theranostics can improve the detection and treatment of cancerous tumors and cardiovascular pathologies such as atherosclerotic plaque [102].…”

Smart Drug Delivery Systems

“…Ultrasound is a highly useful modality for smart therapies, as ultrasound is already in wide clinical use and is readily integrated into clinical practices in a variety of specialties. Moreover, ultrasound-triggered drug delivery vehicles can be combined with ultrasound contrast agents, or microbubbles, to create "theranostic" vehicles; such theranostics incorporate both therapy via drug delivery and diagnostics via imaging [100]. Structurally, microbubbles consist of two components: an encapsulating polymer shell and an inner gas core.…”