Power-Doppler-based NH002 microbubble sonoporation with chemotherapy relieves hypoxia and enhances the efficacy of chemotherapy and immunotherapy for pancreatic tumors.

Pancreatic ductal adenocarcinoma (PDAC) poses challenges due to late-stage diagnosis and limited treatment response, often attributed to the hypoxic tumor microenvironment (TME). Sonoporation, combining ultrasound and microbubbles, holds promise for enhancing therapy. However, additional preclinical research utilizing commercially available ultrasound equipment for PDAC treatment while delving into the TME's intricacies is necessary.

Exploring the Acoustic and Dynamic Characteristics of Phase-Change Droplets.

Acoustic droplet vaporization (ADV) provides the on-demand production of bubbles for use in ultrasound (US)-based diagnostic and therapeutic applications. The droplet-to-bubble transition process has been shown to involve localized internal gas nucleation, followed by a volume expansion of threefold to fivefold and inertial bubble oscillation, all of which take place within a few microseconds. Monitoring these ADV processes is important in gauging the mechanical effects of phase-change droplets in a biological environment, but this is difficult to achieve using regular optical observations.

Ultrasonic Transdermal Delivery System with Acid-Base Neutralization-Generated CO Microbubble Cavitation.

Transdermal delivery systems provide a convenient noninvasive approach for drug administration through the skin, and they have been widely developed for in-home health care. The stratum corneum of the skin surface limits drug penetration, but ultrasound (US)-stimulated microbubble (MB) cavitation can enhance skin permeability to promote transdermal drug penetration. However, the specific materials and complex fabrication of MBs influence the scope of application in transdermal delivery systems.

Monitoring of acoustic cavitation in microbubble-presented focused ultrasound exposure using gradient-echo MRI.

Background: Gadolinium-based contrast agents can be used to identify the blood-brain barrier (BBB) opening after inducing a focused ultrasound (FUS) cavitation effect in the presence of microbubbles. However, the use of gadolinium may be limited for frequent routine monitoring of the BBB opening in clinical applications.

Purpose: To use a gradient-echo sequence without contrast agent administration for monitoring of acoustic cavitation.

Macrophages as Drug Delivery Carriers for Acoustic Phase-Change Droplets.

The major challenges in treating malignant tumors are transport of therapeutic agents to hypoxic regions and real-time assessment of successful drug release via medical imaging modalities. In this study, we propose the use of macrophages (RAW 264.7 cells) as carriers of drug-loaded phase-change droplets to penetrate ischemic or hypoxic regions within tumors.

Camptothecin-loaded fusogenic nanodroplets as ultrasound theranostic agent in stem cell-mediated drug-delivery system.

Adipose-derived stem cells (ADSCs) have been utilized in cellular delivery systems to carry therapeutic agents into tumors by migration. Drug-loaded nanodroplets release drugs and form bubbles after acoustic droplet vaporization (ADV) triggered by ultrasound stimulation, providing a system for ultrasound-induced cellular delivery of theranostic agents. In order to improve the efficiency of drug release, fusogenic nanodroplets were designed to go from nano to micron size upon uptake by ADSCs for reducing ADV threshold.

Characterization of Different Microbubbles in Assisting Focused Ultrasound-Induced Blood-Brain Barrier Opening.

Microbubbles (MBs) serve as a critical catalyst to amplify local cavitation in CNS capillary lumen to facilitate focused ultrasound (FUS) to transiently open the blood-brain barrier (BBB). However, limited understanding is available regarding the effect of different microbubbles to induce BBB opening. The aim of this study is to characterize different MBs on their effect in FUS-induced BBB opening.

Superhydrophobic silica nanoparticles as ultrasound contrast agents.

Microbubbles have been widely studied as ultrasound contrast agents for diagnosis and as drug/gene carriers for therapy. However, their size and stability (lifetime of 5-12min) limited their applications. The development of stable nanoscale ultrasound contrast agents would therefore benefit both.

Focused Ultrasound-Induced Blood-Brain Barrier Opening: Association with Mechanical Index and Cavitation Index Analyzed by Dynamic Contrast-Enhanced Magnetic-Resonance Imaging.

Focused ultrasound (FUS) with microbubbles can temporally open the blood-brain barrier (BBB), and the cavitation activities of microbubbles play a key role in the BBB-opening process. Previous attempts used contrast-enhanced magnetic resonance imaging (CE-MRI) to correlate the mechanical index (MI) with the scale of BBB-opening, but MI only partially gauged acoustic activities, and CE-MRI did not fully explore correlations of pharmacodynamic/pharmacokinetic behaviors. Recently, the cavitation index (CI) has been derived to serve as an indicator of microbubble-ultrasound stable cavitation, and may also serve as a valid indicator to gauge the level of FUS-induced BBB opening.

Inertial cavitation initiated by polytetrafluoroethylene nanoparticles under pulsed ultrasound stimulation.

Nanoscale gas bubbles residing on a macroscale hydrophobic surface have a surprising long lifetime (on the order of days) and can serve as cavitation nuclei for initiating inertial cavitation (IC). Whether interfacial nanobubbles (NBs) reside on the infinite surface of a hydrophobic nanoparticle (NP) and could serve as cavitation nuclei is unknown, but this would be very meaningful for the development of sonosensitive NPs. To address this problem, we investigated the IC activity of polytetrafluoroethylene (PTFE) NPs, which are regarded as benchmark superhydrophobic NPs due to their low surface energy caused by the presence of fluorocarbon.

Real-time monitoring of inertial cavitation effects of microbubbles by using MRI: In vitro experiments.

Purpose: To investigate the feasibility of half-Fourier acquisition single-shot turbo spin-echo (HASTE) for real-time monitoring of signal changes because of water flow induced by inertial cavitation (IC) during microbubbles (MBs)-present focused ultrasound (FUS) exposure.

Theory And Methods: Strong turbulence produced in MB solution at the onset of IC results in the difficulty to refocus signal echoes and thus the decrease in signal intensity (SI). Fundamental investigations were conducted using an agar phantom containing MB dilutions exposed to 1.

Biomimetic Acoustically-Responsive Vesicles for Theranostic Applications.

In recent years, biomimetic cell membrane-derived particles have emerged as a new class of drug delivery system with advantages of biocompatibility, ease of isolation and long circulation profile. Here we report the development and potential theranostic applications of a new biomimetic acoustically-responsive droplet system derived from mammalian red blood cell membrane (RBCM). We hypothesized that drug-loaded RBCM droplets (RBCMDs) would undergo a transition from liquid (droplets) to gas (bubbles) upon high intensity focused ultrasound (HIFU) insonation, resulting in on-demand drug release.

Internal polymer scaffolding in lipid-coated microbubbles for control of inertial cavitation in ultrasound theranostics.

A lipid-polymer composite structure was developed for tuning of inertial cavitation activity of microbubbles under ultrasound exposure. The incorporation of a thin layer of polymer networks inside the lipid monolayer resulted in marked reduction in the inertial cavitation dose. This strategy has the potential to increase the safety of ultrasound theranostic applications assisted by microbubble cavitation.

Targeted tumor theranostics using folate-conjugated and camptothecin-loaded acoustic nanodroplets in a mouse xenograft model.

In this study, we aimed to validate the feasibility of receptor-targeted tumor theranostics with folate-conjugated (FA) and camptothecin-loaded (CPT) acoustic nanodroplets (NDs) (collectively termed FA-CPT-NDs). The ND formulation was based on lipid-stabilized low-boiling perfluorocarbon that can undergo acoustic droplet vaporization (ADV) under ultrasound (US) exposure. Conjugation of folate enhanced the selective delivery to tumors expressing high levels of folate receptor (FR) under mediation by the enhanced permeability and retention effect.

Trapping of a mie sphere by acoustic pulses: effects of pulse length.

The acoustic counterpart of optical tweezers shows great promise as a single-particle manipulator using a highly focused acoustic beam. Understanding the dependence of the trapping performance of the acoustic beam on the acoustic pulse length may facilitate its development and extend the applications. Herein, we propose a ray-based model for the time-course simulation of instantaneous forces exerted on single Mie spheres by highly focused acoustic pulses of arbitrary lengths.

Mechanical bioeffects of acoustic droplet vaporization in vessel-mimicking phantoms.

This study investigated the mechanical bioeffects exerted by acoustic droplet vaporization (ADV) under different experimental conditions using vessel phantoms with a 200-μm inner diameter but different stiffness for imitating the microvasculature in various tumors. High-speed microscopy, passive cavitation detection, and ultrasound attenuation measurement were conducted to determine the morphological characteristics of vascular damage and clarify the mechanisms by which the damage was initiated and developed. The results show that phantom erosion was initiated under successive ultrasound exposure (2 MHz, 3 cycles) at above 8-MPa peak negative pressures (PNPs) when ADV occurred with inertial cavitation (IC), producing lesions whose morphological characteristics were dependent on the amount of vaporized droplets.

Characterization of acoustic droplet vaporization for control of bubble generation under flow conditions.

This study investigated the manipulation of bubbles generated by acoustic droplet vaporization (ADV) under clinically relevant flow conditions. Optical microscopy and high-frequency ultrasound imaging were used to observe bubbles generated by 2-MHz ultrasound pulses at different time points after the onset of ADV. The dependence of the bubble population on droplet concentration, flow velocity, fluid viscosity and acoustic parameters, including acoustic pressure, pulse duration and pulse repetition frequency, was investigated.

Superparamagnetic iron oxide and drug complex-embedded acoustic droplets for ultrasound targeted theranosis.

Ultrasound-triggered acoustic droplet vaporization (ADV) has been reported as a mechanical and chemical theranostic strategy for tumor treatment. However, targeting of sufficient amounts of droplets to solid tumors to direct effective mechanical force toward tumor cells remains a major challenge. In this study, we incorporated superparamagnetic iron oxide (SPIO) nanoparticles into acoustic droplets to allow both magnetism-assisted targeting and magnetic resonance (MR)-guided ultrasound-triggered ADV.

Rapid transformation of protein-caged nanomaterials into microbubbles as bimodal imaging agents.

We present a general method for converting colloidal nanomaterials into microbubbles as ultrasound contrast agents. Protein-caged nanomaterials, made either by self-assembled nanoparticles' protein corona or by fluorescent gold nanoclusters, can be rapidly transformed into microbubbles via a sonochemical route, which promote disulfide cross-linking of cysteine residues between protein-caged nanomaterials and free albumin during acoustic cavitation. The proposed methods yielded microbubbles with multiple functions by adjusting the original nanoparticle/protein mixture.

Ultrasound microbubble contrast agents for diagnostic and therapeutic applications: current status and future design.

Ultrasound contrast agents are highly echogenic microbubbles with many unique properties. Microbubbles can basically improve the sensitivity of conventional ultrasound imaging to the microcirculation. The resonance of microbubbles in response to an incident ultrasound pulse results in nonlinear harmonic emission that serves as the signature of microbubbles in microbubble-specific imaging.

Aptamer-conjugated and drug-loaded acoustic droplets for ultrasound theranosis.

Tumor therapy requires multi-functional treatment strategies with specific targeting of therapeutics to reduce general toxicity and increase efficacy. In this study we fabricated and functionally tested aptamer-conjugated and doxorubicin (DOX)-loaded acoustic droplets comprising cores of liquid perfluoropentane compound and lipid-based shell materials. Conjugation of sgc8c aptamers provided the ability to specifically target CCRF-CEM cells for both imaging and therapy.

Intracellular acoustic droplet vaporization in a single peritoneal macrophage for drug delivery applications.

This study investigated the acoustic droplet vaporization (ADV) of perfluoropentane (PFP) droplets in single droplet-loaded macrophages (DLMs) by insonation with single three-cycle ultrasound pulses. Transient responses of intracellular ADV within a single DLM were observed with synchronous high-speed photography and cavitation detection. Ultrasound B-mode imaging was further applied to demonstrate the contrast enhancement of ADV-generated bubbles from a group of DLMs.

A maleimide-based in-vitro model for ultrasound targeted imaging.

Intricate variations and poor visual access result in the difficulty in studying the property of adherent targeted bubbles using an in vivo model. Here, we propose a simple in-vitro model based on the natural adhesion of maleimide bubbles to gelatin. We validated the maleimide-mediated bubble adhesion using flat gelatin phantoms.

Potential-well model in acoustic tweezers.

Standing-wave acoustic tweezers are popularly used for non-invasive and non-contact particle manipulation. Because of their good penetration in biological tissue, they also show promising prospects for in vivo applications. According to the concept of an optical vortex, we propose an acoustics-vortex- based trapping model of acoustic tweezers.