Dataset Information

Acoustically Driven Microbubbles Enable Targeted Delivery of microRNA-Loaded Nanoparticles to Spontaneous Hepatocellular Neoplasia in Canines.

ABSTRACT: Spatially localized microbubble cavitation by ultrasound offers an effective means of altering permeability of natural barriers (i.e. blood vessel and cell membrane) in favor of nanomaterials accumulation in the target site. In this study, a clinically relevant, minimally invasive ultrasound guided therapeutic approach is investigated for targeted delivery of anticancer microRNA loaded PLGA-b-PEG nanoparticles to spontaneous hepatocellular neoplasia in a canine model. Quantitative assessment of the delivered microRNAs revealed prominent and consistent increase in miRNAs levels (1.5-to 2.3-fold increase (p<0.001)) in ultrasound treated tumor regions compared to untreated control regions. Immunohistology of ultrasound treated tumor tissue presented a clear evidence for higher amount of nanoparticles extravasation from the blood vessels. A distinct pattern of cytokine expression supporting CD8+ T cells mediated "cold-to-hot" tumor transition was evident in all patients. On the outset, proposed platform can enhance delivery of miRNA-loaded nanoparticles to deep seated tumors in large animals to enhance chemotherapy.

SUBMITTER: Kumar SU

PROVIDER: S-EPMC7784952 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Acoustically Driven Microbubbles Enable Targeted Delivery of microRNA-Loaded Nanoparticles to Spontaneous Hepatocellular Neoplasia in Canines.

Kumar Sukumar Uday SU Telichko Arsenii V AV Wang Huaijun H Hyun Dongwoon D Johnson Eric G EG Kent Michael S MS Rebhun Robert B RB Dahl Jeremy J JJ Culp William T N WTN Paulmurugan Ramasamy R

Advanced therapeutics 20201112 12

Spatially localized microbubble cavitation by ultrasound offers an effective means of altering permeability of natural barriers (i.e. blood vessel and cell membrane) in favor of nanomaterials accumulation in the target site. In this study, a clinically relevant, minimally invasive ultrasound guided therapeutic approach is investigated for targeted delivery of anticancer microRNA loaded PLGA-<i>b</i>-PEG nanoparticles to spontaneous hepatocellular neoplasia in a canine model. Quantitative assessm ...[more]

PMID: 33415184

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Project description:BackgroundThere is growing interest in limb contrast-enhanced ultrasound (CEU) perfusion imaging for the evaluation of peripheral artery disease. Because of low resting microvascular blood flow in skeletal muscle, signal enhancement during limb CEU is prohibitively low for real-time imaging. The aim of this study was to test the hypothesis that this obstacle can be overcome by intermediate- rather than low-power CEU when performed with an acoustically resilient microbubble agent.MethodsViscoelastic properties of Definity and Sonazoid were assessed by measuring bulk modulus during incremental increases in ambient pressure to 200 mm Hg. Comparison of in vivo microbubble destruction and signal enhancement at a mechanical index (MI) of 0.1 to 0.4 was performed by sequential reduction in pulsing interval from 10 to 0.05 sec during limb CEU at 7 MHz in mice and 1.8 MHz in dogs. Destruction was also assessed by broadband signal generation during passive cavitation detection. Real-time CEU perfusion imaging with destruction-replenishment was then performed at 1.8 MHz in dogs using an MI of 0.1, 0.2, or 0.3.ResultsSonazoid had a higher bulk modulus than Definity (66 ± 12 vs 29 ± 2 kPa, P = .02) and exhibited less inertial cavitation (destruction) at MIs ≥ 0.2. On in vivo CEU, maximal signal intensity increased incrementally with MI for both agents and was equivalent between agents except at an MI of 0.1 (60% and 85% lower for Sonazoid at 7 and 1.8 MHz, respectively, P < .05). However, on progressive shortening of the pulsing interval, Definity was nearly completely destroyed at MIs ≥ 0.2 at 1.8 and 7 MHz, whereas Sonazoid was destroyed only at 1.8 MHz at MIs ≥ 0.3. As a result, real-time CEU perfusion imaging demonstrated approximately fourfold greater enhancement for Sonazoid at an MI of 0.3 to 0.4.ConclusionsRobust signal enhancement during real-time CEU perfusion imaging of the limb is possible when using intermediate-power imaging coupled with a durable microbubble contrast agent.

Dataset Information

Acoustically Driven Microbubbles Enable Targeted Delivery of microRNA-Loaded Nanoparticles to Spontaneous Hepatocellular Neoplasia in Canines.

Publications

Acoustically Driven Microbubbles Enable Targeted Delivery of microRNA-Loaded Nanoparticles to Spontaneous Hepatocellular Neoplasia in Canines.

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