Development of three-dimensional lung multicellular spheroids in air- and liquid-interface culture for the evaluation of anticancer therapeutics

Samantha A. Meenach, Alexandra N. Tsoras, Ronald C. McGarry, Heidi M. Mansour, J. Zach Hilt, Kimberly W. Anderson

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Three-dimensional (3D) lung multicellular spheroids (MCS) in liquid-covered culture (LCC) and air-interface culture (AIC) conditions have both been developed for the evaluation of aerosol anticancer therapeutics in solution and aerosols, respectively. The MCS were formed by seeding lung cancer cells on top of collagen where they formed spheroids due to the prevalence of cell-to-cell interactions. LCC MCS were exposed to paclitaxel (PTX) in media whereas AIC MCS were exposed to dry powder PEGylated phospholipid aerosol microparticles containing paclitaxel. The difference in viability for 2D versus 3D culture for both LCC and AIC was evaluated along with the effects of the particles on lung epithelium via transepithelial electrical resistance (TEER) measurements. For LCC and AIC conditions, the 3D spheroids were more resistant to treatment with higher IC50 values for A549 and H358 cell lines. TEER results initially indicated a decrease in resistance upon drug or particle exposure, however, these values increased over the course of several days indicating the ability of the cells to recover. Overall, these studies offer a comprehensive in vitro evaluation of aerosol particles used in the treatment of lung cancer while introducing a new method for culturing lung cancer MCS in both LCC and AIC conditions.

Original languageEnglish
Pages (from-to)1701-1709
Number of pages9
JournalInternational Journal of Oncology
Issue number4
StatePublished - Apr 2016

Bibliographical note

Funding Information:
The authors gratefully acknowledge financial support from the National Cancer Institute (NCI) grant no. R25CA153954 and a National Cancer Institute Cancer Nanotechnology Training Center (NCI-CNTC) Postdoctoral Traineeship awarded to S.A.M. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.


  • air interface culture
  • lung cancer
  • multicellular spheroids
  • paclitaxel
  • three-dimensional cell culture

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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