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Charge-reversal-functionalized PLGA nanobubbles as theranostic agents for ultrasonic-imaging-guided combination

Hong Yang1, Xue Shen, Jie Yan

  • 1Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, China. liuyiyao@uestc.edu.cn liuyiyao@hotmail.com.

Biomaterials Science
|July 25, 2018
PubMed

Insights

This study introduces novel nanobubbles that deliver chemotherapy and P-gp shRNA to overcome cancer drug resistance. The nanobubbles show enhanced tumor inhibition and imaging capabilities, offering a promising strategy for resistant cancer therapy.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Multiple drug resistance (MDR) in cancer limits chemotherapy efficacy, often due to ATP-binding cassette (ABC) transporter proteins like P-glycoprotein (P-gp).
  • Innovative strategies are needed to reverse MDR and improve cancer treatment outcomes.

Purpose of the Study:

  • To develop and evaluate novel charge-reversal-functionalized PLGA nanobubbles (Dox-NBs/PPP/P-gp shRNA) for co-delivering doxorubicin (Dox) and P-gp shRNA.
  • To assess the potential of these nanobubbles for drug resistance reversal, ultrasonic-imaging-guided tumor therapy, and overcoming MDR in cancer.

Main Methods:

  • Characterization of nanobubbles using techniques like 1H NMR, FT-IR, SEM, DLS, and UV-vis spectroscopy.
  • In vitro evaluation of drug delivery, P-gp expression suppression, and therapeutic effects on MCF-7/MDR cells.
  • In vivo antitumor assays in tumor-bearing nude mice and assessment of biocompatibility and systemic toxicity.
  • In vivo ultrasonic imaging to evaluate nanobubble contrast agent properties.

Main Results:

  • The Dox-NBs/PPP/P-gp shRNA nanobubbles demonstrated pH-responsive release, good dispersity, and biocompatibility.
  • Co-delivery of Dox and P-gp shRNA effectively suppressed P-gp expression and drug efflux in vitro, enhancing therapeutic effects.
  • In vivo studies showed a 65% inhibition rate against MCF-7/ADR tumors with reduced side effects and negligible systemic toxicity.
  • The nanobubbles served as an efficient contrast agent for ultrasonic imaging of solid tumors.

Conclusions:

  • The developed nanobubbles are effective in co-delivering chemotherapy drugs and P-gp shRNA to overcome MDR.
  • This approach significantly enhances antitumor efficacy and offers potential for imaging-guided combination therapy in resistant cancers.
  • The nanocarrier system exhibits high biocompatibility and reduced systemic toxicity, highlighting its therapeutic promise.

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