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

Pei-Sin Yang1, Fu-I Tung2, Hsiao-Ping Chen1

  • 1Institute of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan, ROC.

Acta Biomaterialia
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New carboxymethyl hexanoyl chitosan (CHC) bubbles loaded with superparamagnetic iron oxide (SPIO) nanoparticles enable image-guided delivery of hydrophobic drugs to tumors. These novel CHC/SPIO nanobubbles enhance drug delivery and reduce side effects for targeted cancer therapy.

Keywords:
Bubble-forming materialsCarboxymethyl hexanoyl chitosanSPIOSonicationTheranostic

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Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Drug Delivery Systems
  • Medical Imaging

Background:

  • Hydrophobic drugs face challenges in tumor delivery due to poor solubility and systemic toxicity.
  • Image-guided drug delivery systems are crucial for targeted cancer therapy.
  • Chitosan-based materials offer biocompatibility and versatility in biomedical applications.

Purpose of the Study:

  • To develop novel image-guided nanobubbles (NBs) for efficient encapsulation and delivery of hydrophobic agents to tumor cells.
  • To utilize carboxymethyl hexanoyl chitosan (CHC) and superparamagnetic iron oxide (SPIO) nanoparticles for dual-modality imaging and therapy.
  • To evaluate the in vitro and in vivo efficacy of CHC/SPIO NBs for targeted cancer treatment.

Main Methods:

  • Preparation of micronized bubbles (CHC/SPIO MBs) for ultrasound imaging and nanosized bubbles (CHC/SPIO NBs) for magnetic resonance imaging (MRI).
  • Optimization of SPIO nanoparticle and hexane amounts for CHC/SPIO NB synthesis.
  • In vitro evaluation of camptothecin (CPT)-loaded CHC/SPIO NBs for cellular delivery and cytotoxicity using therapeutic sonication.
  • In vivo study involving intratumoral injection of DiR-loaded CHC/SPIO NBs in mice, with distribution tracked by near-infrared (NIR) imaging.

Main Results:

  • CHC/SPIO MBs exhibited ultrasound imaging functionality, while CHC/SPIO NBs provided MRI T2 contrast.
  • CPT-loaded CHC/SPIO NBs demonstrated significantly enhanced transcellular delivery and cytotoxicity compared to free CPT in vitro.
  • Intratumoral injection of DiR-loaded CHC/SPIO NBs resulted in significant tumor-specific accumulation in vivo, unlike free DiR.

Conclusions:

  • Novel CHC/SPIO NBs are effective for image-guided encapsulation and delivery of hydrophobic agents.
  • This approach enhances drug efficacy and cellular uptake while potentially reducing therapeutic agent dosage and side effects.
  • CHC/SPIO NBs hold promise for future targeted cancer therapies combining local delivery, imaging, and enhanced drug action.