Acoustically Driven Microbubbles Enable Targeted Delivery of microRNA‐Loaded Nanoparticles to Spontaneous Hepatocellular Neoplasia in Canines. Issue 12 (12th November 2020)

• Record Type: Journal Article
• Authors: Kumar, Sukumar Uday; Telichko, Arsenii V.; Wang, Huaijun; Hyun, Dongwoon; Johnson, Eric G.; Kent, Michael S.; Rebhun, Robert B.; Dahl, Jeremy J.; Culp, William T. N.; Paulmurugan, Ramasamy
• Is Part Of: Advanced therapeutics. Volume 3:Issue 12(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-11-12
• Subjects: dog model -- focused ultrasound -- microbubbles -- microRNA -- nanoparticles -- targeted delivery; Therapeutics -- Periodicals; Pharmaceutical technology -- Periodicals; Pharmacogenetics -- Periodicals; 615.5
• DOI: 10.1002/adtp.202000120
• Languages: English
• ISSNs: 2366-3987

Abstract

Abstract: Spatially localized microbubble cavitation by ultrasound offers an effective means of altering the permeability of natural barriers (i.e., blood vessels and cell membranes) in favor of nanomaterial accumulation in target sites. In this study, a clinically relevant, minimally invasive ultrasound guided therapeutic approach is investigated for the targeted delivery of anticancer microRNA loaded PLGA‐ b ‐PEG nanoparticles to spontaneous hepatocellular neoplasia in a canine model. Quantitative assessment of the delivered microRNAs reveals a prominent and consistent increase in microRNAs levels (1.5‐ to 2.3‐fold increase [ p < 0.001]) in ultrasound treated tumor regions compared to untreated control regions. The immunohistology of ultrasound treated tumor tissue presents clear evidence for a higher amount of nanoparticle extravasation from the blood vessels. A distinct pattern of cytokine expression supporting a CD8+ T cells mediated "cold‐to‐hot" tumor transition is evident in all patients. This proposed platform can enhance delivery of microRNA‐loaded nanoparticles to deeply located visceral tumors in large animals to enhance chemotherapy. Abstract : This work describes a non‐invasive means of altering the permeability of natural barriers in favor of nanomaterial accumulation in the target tissues by ultrasound triggered microbubble cavitation. A single curvilinear ultrasound array transducer with clinical‐grade SonoVue microbubble enhances anticancer microRNA loaded PLGA‐ b ‐PEG ultrasound delivery by 1.5‐to 2.3‐fold in canines with spontaneously occurring hepatocellular neoplasia.