Development and Evaluation of Air-Grown Lung Cancer Spheroids

DEVELOPMENT AND EVALUATION OF AIR-GROWN LUNG CANCER SPHEROIDS

Nicholas J. Fraunfelter¹, Elisa A. Torrico-Guzman¹, Sweta K. Gupta¹, Samantha A. Meenach^1,2

¹Department of Chemical Engineering, ²Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI

2015 AIChE Annual Conference, Salt Lake City, UT, November 6 – November 9

Lung cancer has the highest mortality rate of any type of cancer, with an estimated 160,000 deaths in the U.S. alone in 2014. This number can be partially attributed to the limitations in the proper evaluation of chemotherapeutics in vitro, which leads to high costs in drug development and an unsatisfactory success rate of drug candidates. Three-dimensional (3D) multicellular spheroid models (MCS) have recently gained attention in the testing of chemotherapeutics since they more accurately portray tumors by exhibiting intrinsic physiological and morphological characteristics similar to tumor tissue. Currently, anti-cancer agents are evaluated on two-dimensional cancer cells in liquid culture during the drug development process. Aerosol therapeutics targeting tumors in the air pathways of the lungs are not accurately evaluated in liquid culture and thus there is an urgent need for an in vitro model to overcome this limitation.

A more appropriate model has been developed here; it will allow for 3D lung cancer MCS to be grown in air-interface culture in order to evaluate aerosol anti-cancer agents in a high-throughput fashion. Cells were seeded into a hydrogel mold comprised of a non-interactive, degradable biopolymer, alginate, within a Transwell. Solid spheroids formed quickly and uniformly, via gravity, in the alginate hydrogel molds. The alginate was degraded using ethylenediaminetetraacetic acid (EDTA) after the spheroids formed in the alginate molds, which left the lung cancer spheroids in contact with media on their basolateral side only and the remaining bulk of the spheroids exposed to air.

The alginate hydrogels used were optimized to achieve a Young’s modulus mimicking lung tissue. Varying the molecular weight and concentration of crosslinker allowed for the control of the mechanical properties of alginate hydrogels. Overall, air-grown lung cancer MCS would be an excellent tool for the screening aerosolized anti-cancer agents. This new in vitro model can decrease the cost and time involved in the drug development process.