Breaking free from vascular confinement: status and prospects for submicron ultrasound contrast agents

Abstract

The development of encapsulated microbubbles (~1-6 μm) has expanded the utility of ultrasound from soft tissue anatomical imaging to not only functional intravascular imaging, but therapeutic interventions, with compelling studies of elicited biological effects. The large diameter of these bubbles has confined their utility to the vasculature, but converging interdisciplinary research pathways are giving rise to new submicron ultrasound contrast agents capable of extending their effects beyond the vascular compartment. This article reviews the status and prospects of exogenous agents including nanobubbles, echogenic liposomes, gas vesicles, cavitation seeds, and nanodroplets, and assesses outstanding criticisms preventing their advance. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Investigating the optimum size of nanoparticles for their delivery into the brain assisted by focused ultrasound-induced blood–brain barrier opening

“…For brain tumor, metastasis caused by FUS-induced damage and bleeding of tumor could be a further concern. We believe that the interactive co-development of drug carriers, MBs 58 – 60 , and FUS equipment to create an entire system will lead to safe, novel therapeutic strategies for CNS diseases.…”

How Nanomedicine Can Be Used in the Treatment of Tumors: an Interview With Dr Gang Zheng

“…Moreover, our group discovered that, under similar ultrasound exposures, porphyrin microbubbles can undergo an in situ conversion into nano-sized bubbles [4]. This discovery enables the development of a novel EPR-independent nanoparticle delivery strategy in which co-administration of ultrasound and systemically injected microbubbles would both locally generate porphyrin nanoparticles while also increasing vascular leakiness, allowing for combined tumor imaging and therapy [5]. Both light and ultrasound-enabled strategies described above offer an alternative to the EPR-centered delivery paradigm used ubiquitously thus far, promising more predictable and controlled tumor nanomedicine delivery.…”

Improving accessibility of EPR-insensitive tumor phenotypes using EPR-adaptive strategies: Designing a new perspective in nanomedicine delivery

“…A. Cavitation-based mechanisms by which ultrasound can enhance nanomedicine delivery, including transient disruption through stable cavitation and destructive opening through inertial cavitation (adapted from 157). B. Co-injection involves simultaneous administration of microbubbles and nanoparticles with ultrasound priming to improve delivery.…”