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Probing drug delivery and mechanisms of action in 3D spheroid cells by quantitative analysis

Authors
Heo, Chae EunHong, AreumKim, MinjiLee, Jong WhaChae, Soo YeonSung, Ki WoongLee, Ji WonHeo, Sung WooKim, Hugh, I
Issue Date
7-12월-2020
Publisher
ROYAL SOC CHEMISTRY
Citation
ANALYST, v.145, no.23, pp.7687 - 7694
Indexed
SCIE
SCOPUS
Journal Title
ANALYST
Volume
145
Number
23
Start Page
7687
End Page
7694
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/50832
DOI
10.1039/d0an01518k
ISSN
0003-2654
Abstract
Human tumor cells in a 3-dimensional (3D) spheroid can reflect the characteristics of solid tumors by forming cell-cell interactions and microenvironments. This makes 3D cell culture useful for preclinical stability and drug efficacy tests. In this study, the drug delivery and action mechanisms in SK-N-SH neuroblastoma cells cultured in 3D spheroids were quantitatively compared to those cultured in 2D monolayers using confocal microscopy imaging and inductively coupled plasma-mass spectrometry. In the 3D spheroids, cisplatin only accessed the surface, accumulating in the cells on the spheroid exterior. As a result, an increased cellular amount of cisplatin was required to obtain similar cytotoxicity in the 3D spheroid cells to that in 2D monolayers. The mechanisms of reduction of drug efficacy by dimethyl sulfoxide (DMSO) in the 3D spheroid cells compared to those in the 2D monolayer cells were further investigated. DMSO reduced the drug cytotoxicity by forming stable DMSO-substituted compounds that inhibited the cellular uptake of cisplatin and DNA-Pt adduct formation. The quantitative analysis used in this study is promising for understanding drug delivery and drug action mechanisms in cells in various microenvironments.
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