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

Sukumar Uday Kumar, Arsenii V. Telichko, Huaijun Wang, Dongwoon Hyun, Eric G. Johnson, Michael S. Kent, Robert B Rebhun, Jeremy J. Dahl, William T.N. Culp, Ramasamy Paulmurugan

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Article number2000120
JournalAdvanced Therapeutics
Volume3
Issue number12
DOIs
StatePublished - Dec 2020

Keywords

  • dog model
  • focused ultrasound
  • microbubbles
  • microRNA
  • nanoparticles
  • targeted delivery

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, medical
  • Pharmacology (medical)
  • Genetics(clinical)
  • Pharmaceutical Science
  • Pharmacology

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