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Response of heterogeneous cancer cells on targeted nanoparticles

Ying Wang1, Yingjia Li2, Dongxiao Wang3

  • 1Guangdong Provincial Key laboratory of cancer immunotherapy Research, Guangzhou Key Laboratory of Tumor Immunology Research, Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University.

Nanomedicine : Nanotechnology, Biology, and Medicine
|June 6, 2016
PubMed

Insights

Targeted nanoparticles carrying Rh123 effectively target the drug-resistant, quiescent cancer cell population (Rh123low). These nanoparticles bypass efflux mechanisms, offering a promising strategy against multidrug resistance (MDR).

Area of Science:

  • Cancer Biology
  • Nanomedicine
  • Drug Delivery

Background:

  • Heterogeneous cancer cells exhibit multidrug resistance (MDR) linked to quiescence and ABC-transporter activity.
  • The Rh123 exclusion assay identifies a quiescent, drug-resistant subpopulation (Rh123low).

Purpose of the Study:

  • To investigate the efficacy of Rh123-loaded targeted nanoparticles (Rh123 NPs) against the Rh123low cancer cell population.
  • To elucidate the role of ABC-transporters in the uptake and efflux of Rh123 and Rh123 NPs.

Main Methods:

  • Fabrication of targeted nanoparticles loaded with Rhodamine 123 (Rh123 NPs).
  • Utilizing the Rh123 exclusion assay to identify and analyze the Rh123low population.
  • Assessing the uptake and efflux of Rh123 and Rh123 NPs in cancer cells, with a focus on ABC-transporter activity.

Main Results:

  • Rh123 NPs effectively stained the Rh123low population, mirroring the heterogeneity observed with free Rh123.
  • ABC-transporters did not influence the uptake of Rh123 or Rh123 NPs.
  • While ABC-transporters mediated Rh123 efflux, Rh123 NPs were not susceptible, suggesting a mechanism to overcome MDR.
  • Targeted delivery and endocytosis of Rh123 NPs were key to enhanced cellular uptake.

Conclusions:

  • Targeted nanoparticles offer a novel approach to overcome cancer multidrug resistance by effectively targeting the quiescent Rh123low cell population.
  • Rh123 NPs bypass ABC-transporter-mediated efflux, highlighting their potential for improved therapeutic outcomes in MDR cancers.
Keywords:
Heterogenous cancer cellsMDRRh123Targeted nanoparticles

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