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Sample Extraction and Simultaneous Chromatographic Quantitation of Doxorubicin and Mitomycin C Following Drug Combination Delivery in Nanoparticles to Tumor-bearing Mice
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Folate-mediated mitochondrial targeting with doxorubicin-polyrotaxane nanoparticles overcomes multidrug resistance

He Wang1,2, Henghui Yin3, Fengjiao Yan4

  • 1Department of Oncology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.

Oncotarget
|January 22, 2015
PubMed

Insights

New functional doxorubicin (DOX) nanoparticles overcome drug resistance in cancer therapy. These targeted nanoparticles show enhanced anticancer efficacy by inducing apoptosis in resistant tumor cells.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Therapy

Background:

  • Anticancer drug resistance is a major challenge in cancer treatment, leading to therapeutic failure.
  • Doxorubicin (DOX) is a widely used cytotoxic drug, but its efficacy is limited by drug resistance.

Purpose of the Study:

  • To develop functional doxorubicin (DOX) nanoparticles for targeted delivery to overcome cancer drug resistance.
  • To evaluate the anticancer efficacy and mechanism of action of these novel DOX nanoparticles.

Main Methods:

  • Functional DOX nanoparticles were synthesized using folate-terminated polyrotaxanes and dequalinium.
  • Nanoparticle characterization included size (approx. 101 nm), zeta potential (3.25 mV), and drug loading (18%).
  • Anticancer efficacy was assessed in vitro and in a drug-resistant MCF-7/Adr xenograft tumor model.

Main Results:

  • Functional DOX nanoparticles demonstrated superior anticancer efficacy compared to free DOX and other nanoparticle formulations.
  • These nanoparticles significantly increased intracellular DOX uptake, accumulating in mitochondria and endoplasmic reticulum.
  • Apoptosis was induced via activation of caspase-9 and caspase-3, mitochondrial pathway involvement, and modulation of Bcl-2 family proteins.

Conclusions:

  • Functional DOX nanoparticles offer a promising strategy to enhance DOX solubility and overcome multidrug resistance in cancer.
  • Targeted delivery of DOX via these nanoparticles effectively induces apoptosis in resistant cancer cells.

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