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A novel bubble-forming material for preparing hydrophobic-agent-loaded bubbles with theranostic functionality.

Abstract
In the present study, a new bubble-forming material (carboxymethyl hexanoyl chitosan, CHC), together with superparamagnetic iron oxide (SPIO) nanoparticles, was employed to prepare image-guided bubbles for efficiently encapsulating and delivering hydrophobic agents to kill tumor cells. The results showed that CHC could be used for preparing not only micronized bubbles (CHC/SPIO MBs) to exhibit ultrasound imaging functionality but also nanosized bubbles (CHC/SPIO NBs) to exhibit magnetic resonance T2 image contrast. It was found that the amounts of SPIO nanoparticles and hexane during preparation process were the key factors to obtaining CHC/SPIO NBs. Most importantly, under in vitro cell culture conditions with the same amount of camptothecin (CPT) and therapeutic sonication, CPT-loaded CHC/SPIO NBs demonstrated more significant transcellular delivery and cytotoxicity than free CPT. Subsequently, an intratumoral injection was proposed for the in vivo administration of hydrophobic-agent-loaded CHC/SPIO NBs. After injection, the distribution of a hydrophobic dye (DiR, an agent with near-infrared (NIR) fluorescence used as a model drug) released from the CHC/SPIO NBs was tracked by an NIR imaging technique. A significant tumor-specific accumulation was observed in the mouse that received the DiR-loaded CHC/SPIO NBs; the same was not observed in the mouse that received the free dye (without incorporating with CHC/SPIO NBs). It is expected, in the future, both the dose of the therapeutic agent administered and its side effects can be significantly lowered by using novel CHC/SPIO NBs together with local delivery (intratumoral injection), targeted imaging and enhanced cellular uptake of the drug.
AuthorsPei-Sin Yang, Fu-I Tung, Hsiao-Ping Chen, Tse-Ying Liu, Yi-Ying Lin
JournalActa biomaterialia (Acta Biomater) Vol. 10 Issue 8 Pg. 3762-74 (Aug 2014) ISSN: 1878-7568 [Electronic] England
PMID24830551 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Chemical References
  • Contrast Media
  • Dextrans
  • Gases
  • Magnetite Nanoparticles
  • ferumoxtran-10
Topics
  • Animals
  • Breast Neoplasms (pathology, therapy)
  • Cell Line, Tumor
  • Contrast Media (chemistry)
  • Dextrans (chemistry)
  • Female
  • Gases (chemical synthesis)
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Magnetic Resonance Imaging (methods)
  • Magnetite Nanoparticles (chemistry)
  • Mice
  • Mice, Nude
  • Microbubbles (therapeutic use)
  • Treatment Outcome
  • Ultrasonic Therapy (methods)

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