3D lung spheroid cultures for evaluation of photodynamic therapy (PDT) procedures in microfluidic Lab-on-a-Chip system

Anal Chim Acta. 2017 Oct 16:990:110-120. doi: 10.1016/j.aca.2017.07.009. Epub 2017 Jul 14.

Abstract

The purpose of this paper is to present a fully integrated microchip for the evaluation of PDT procedures efficiency on 3D lung spheroid cultures. Human lung carcinoma A549 and non-malignant MRC-5 spheroids were utilized as culture models. Spheroid viability was evaluated 24 h after PDT treatment, in which 5-aminolevulinic acid (ALA) had been used as a precursor of a photosensitizer (protoporphyrin IX - PpIX). Moreover, spheroid viability over a long-term (10-day) culture was also examined. We showed that the proposed PDT treatment was toxic only for cancer spheroids. This could be because of a much-favoured enzymatic conversion of ALA to PpIX in cancer as opposed normal cells. Moreover, we showed that to obtain high effectiveness of ALA-PDT on lung cancer spheroids additional time of spheroid after light exposure was required. It was found that PDT had been effective 5 days after PDT treatment with 3 mM ALA. To the best of our knowledge this has been the first presentation of such research performed on a 3D lung spheroids culture in a microfluidic system.

Keywords: 3D culture model; Lung cells; Photocytotoxicity; Photodynamic therapy (PDT); Reactive oxygen species; Spheroids.

MeSH terms

  • A549 Cells
  • Aminolevulinic Acid / chemistry*
  • Humans
  • Lab-On-A-Chip Devices*
  • Lung Neoplasms / drug therapy
  • Photochemotherapy*
  • Photosensitizing Agents / chemistry*
  • Protoporphyrins / chemistry*
  • Spheroids, Cellular / drug effects*

Substances

  • Photosensitizing Agents
  • Protoporphyrins
  • Aminolevulinic Acid