Fibrin-Targeted Polymerized Shell Microbubbles as Potential Theranostic Agents for Surgical Adhesions

Langmuir. 2019 Aug 6;35(31):10061-10067. doi: 10.1021/acs.langmuir.8b03692. Epub 2019 Feb 8.

Abstract

The development of new therapies for surgical adhesions has proven to be difficult as there is no consistently effective way to assess treatment efficacy in clinical trials without performing a second surgery, which can result in additional adhesions. We have developed lipid microbubble formulations that use a short peptide sequence, CREKA, to target fibrin, the molecule that forms nascent adhesions. These targeted polymerized shell microbubbles (PSMs) are designed to allow ultrasound imaging of early adhesions for diagnostic purposes and for evaluating the success of potential treatments in clinical trials while acting as a possible treatment. In this study, we show that CREKA-targeted microbubbles preferentially bind fibrin over fibrinogen and are stable for long periods of time (∼48 h), that these bound microbubbles can be visualized by ultrasound, and that neither these lipid-based bubbles nor their diagnostic-ultrasound-induced vibrations damage mesothelial cells in vitro. Moreover, these bubbles show the potential to identify adhesionlike fibrin formations and may hold promise in blocking or breaking up fibrin formations in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Survival / drug effects
  • Contrast Media / chemistry*
  • Contrast Media / toxicity
  • Fibrin / metabolism*
  • Humans
  • Lab-On-A-Chip Devices
  • Microbubbles*
  • Microfluidics / instrumentation
  • Microfluidics / methods
  • Oligopeptides / chemistry
  • Oligopeptides / metabolism
  • Oligopeptides / toxicity
  • Phosphatidylcholines / chemistry
  • Phosphatidylcholines / toxicity
  • Phosphatidylethanolamines / chemistry
  • Phosphatidylethanolamines / toxicity
  • Polyacetylene Polymer / chemical synthesis
  • Polyacetylene Polymer / chemistry
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / toxicity
  • Theranostic Nanomedicine / methods
  • Tissue Adhesions / diagnostic imaging*
  • Ultrasonography / methods

Substances

  • 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000)
  • Contrast Media
  • Oligopeptides
  • Phosphatidylcholines
  • Phosphatidylethanolamines
  • Polyacetylene Polymer
  • cysteinyl-arginyl-glutamyl-lysyl-alanyl
  • polydiacetylene
  • Polyethylene Glycols
  • Fibrin