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

Nanomedicine : nanotechnology, biology, and medicine (2015-03-11)
AhRan Kang, Hye In Seo, Bong Geun Chung, Sang-Hoon Lee
ABSTRACT

We investigated the effect of anticancer drug-loaded functional polymeric nanoparticles on drug resistance of three-dimensional (3D) breast tumor spheroids. 3D tumor models were built using concave microwells with different diameters (300-700μm) and nanoparticles were prepared using thermo-responsive poly(N-isopropylacrylamide) (PNIPAM)-co-acrylic acid (AA). Upon culturing with doxorubicin-loaded PNIPAM-co-AA nanoparticles for 96hours, the smallest tumor spheroids were extensively disrupted, resulting in a reduction in spheroid diameter. In contrast, the sizes of the largest tumor spheroids were not changed. Scanning electron microscopy revealed that the circular shape of 3D spheroids treated with doxorubicin-loaded PNIPAM-co-AA nanoparticles had collapsed severely. Cell viability assays also demonstrated that the largest tumor spheroids cultured with doxorubicin-loaded PNIPAM-co-AA nanoparticles were highly resistant to the anticancer drug. We confirmed that tight cell-cell contacts within largest tumor spheroids significantly improved the anticancer drug resistance. Therefore, this uniform-sized 3D breast tumor model could be a potentially powerful tool for anticancer drug screening applications. The battle against cancer is a big challenge. With new anti-cancer drugs being developed under the nanotechnology platform, there is a need to have a consistent and reliable testing system that mimics the in-vivo tumor scenario. The authors successfully designed a 3D tumor model using concave microwells to produce different tumor diameters. This will be of value for future drug screening.

MATERIALS
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Product Description

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