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Concave microwell array-mediated three-dimensional tumor model for screening anticancer drug-loaded nanoparticles.

AhRan Kang1, Hye In Seo2, Bong Geun Chung2

  • 1NBIT, KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, Republic of Korea.

Nanomedicine : Nanotechnology, Biology, and Medicine
|March 11, 2015
PubMed
Summary

Functional polymeric nanoparticles loaded with anticancer drugs show varying effects on 3D breast tumor spheroids. Smaller spheroids were disrupted, while larger ones exhibited drug resistance due to tight cell-cell contacts, highlighting a new drug screening model.

Keywords:
Anticancer drug screeningConcave microwell arrayPolymeric nanoparticleThree-dimensional tumor modelUniform-sized tumor

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Area of Science:

  • Nanotechnology
  • Materials Science
  • Biomedical Engineering

Background:

  • Developing effective cancer therapies requires reliable in-vivo mimicking tumor models for drug screening.
  • Nanotechnology offers novel platforms for targeted drug delivery and cancer treatment.

Purpose of the Study:

  • To investigate the impact of anticancer drug-loaded functional polymeric nanoparticles on drug resistance in 3D breast tumor spheroids.
  • To evaluate the utility of a 3D tumor model for anticancer drug screening.

Main Methods:

  • Fabrication of 3D breast tumor spheroids using concave microwells of varying diameters (300-700μm).
  • Preparation of thermo-responsive poly(N-isopropylacrylamide) (PNIPAM)-co-acrylic acid (AA) nanoparticles loaded with doxorubicin.
  • Treatment of 3D tumor spheroids with drug-loaded nanoparticles and subsequent analysis of spheroid disruption, size changes, and cell viability.

Main Results:

  • Doxorubicin-loaded nanoparticles significantly disrupted smaller 3D tumor spheroids.
  • Larger 3D tumor spheroids exhibited resistance to the anticancer drug, showing no significant size reduction.
  • Scanning electron microscopy confirmed severe collapse in treated spheroid shapes.
  • Cell viability assays indicated high drug resistance in larger spheroids, attributed to tight cell-cell contacts.

Conclusions:

  • Tight cell-cell contacts in larger 3D breast tumor spheroids significantly enhance anticancer drug resistance.
  • Uniform-sized 3D breast tumor models are a promising tool for effective anticancer drug screening applications.