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Manipulating multifaceted microbubble shell composition to target both TRAIL-sensitive and resistant cells.

Lauren J Jablonowski1, Dolores Conover1, Nutte T Teraphongphom1

  • 1School of Biomedical Engineering, Science, and Health Systems, Drexel University, 3141 Chestnut Street, Philadelphia, Pennsylvania, 19104.

Journal of Biomedical Materials Research. Part A
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Summary

This study developed novel ultrasound-responsive microbubbles for targeted cancer therapy. Co-encapsulating TRAIL and doxorubicin demonstrated significant cell death in both sensitive and resistant breast cancer cells.

Keywords:
TRAILmicrobubbleshell propertiestargeted drug deliveryultrasound

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Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Cancer Therapy

Background:

  • Targeted drug delivery agents are crucial for effective cancer treatment.
  • Ultrasound-responsive microbubbles offer a promising platform for localized drug release.
  • Combining TRAIL (TNF-related apoptosis-inducing ligand) and doxorubicin presents a potential strategy to overcome drug resistance.

Purpose of the Study:

  • To develop and evaluate ultrasound-responsive microbubbles co-encapsulating TRAIL and doxorubicin for cancer therapy.
  • To investigate the impact of polymeric shell composition on drug delivery efficacy.
  • To assess the effectiveness against TRAIL-sensitive and TRAIL-resistant breast cancer cells.

Main Methods:

  • Fabrication of ultrasound-responsive microbubbles with varying polymeric shell compositions (e.g., PLA, LipidPEG).
  • Co-encapsulation of TRAIL and doxorubicin within the microbubble shells.
  • In vitro assessment of cell death (apoptosis and necrosis) in MDA-MB-231 and MCF7 cell lines upon ultrasound exposure.
  • Comparison of nanoshard effects versus whole microbubbles.

Main Results:

  • Ultrasound-triggered nanoshards demonstrated significant apoptotic cell death, with efficacy dependent on shell composition.
  • Co-encapsulation of doxorubicin induced necrosis, with PEGylation showing reduced effectiveness.
  • Combined TRAIL and doxorubicin delivery significantly increased cell death in MDA-MB-231 cells (40-80%) and sensitized TRAIL-resistant MCF7 cells (30-60%).

Conclusions:

  • Ultrasound-responsive microbubbles are effective targeted drug delivery agents for cancer therapy.
  • Co-encapsulation of TRAIL and doxorubicin provides a multifaceted approach to enhance cancer cell death.
  • This technology offers a promising strategy for treating solid tumors, potentially overcoming drug resistance.