A Spheroid‐Forming Hybrid Gold Nanostructure Platform That Electrochemically Detects Anticancer Effects of Curcumin in a Multicellular Brain Cancer Model

• Published in: Small (Weinheim an der Bergstrasse, Germany) Germany), 2021-04, Vol.17 (15), p.e2002436-n/a
• Main Authors: Suhito, Intan Rosalina, Angeline, Novi, Lee, Kwang‐Ho, Kim, Huijung, Park, Chun Gwon, Luo, Zhengtang, Kim, Tae‐Hyung
• Format: Article
• Language: English
• Subjects: Anticancer properties; Brain; Brain cancer; Cancer; Cell adhesion; Colorimetry; Cultivation; drug screening; electrochemical detection; Gold; gold nanostructures; multicellular spheroids; Nanostructure; Nanotechnology; Spheroids
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.202002436

In this study, a multifunctional platform that enables the highly efficient formation of 3D multicellular cancer spheroids and precise real‐time assessments of the anticancer effects of curcumin in a brain tumor coculture model is reported. A highly conductive gold nanostructure (HCGN) is fabricated to facilitate cancer spheroid formation without using anti‐cell adhesion molecules. A neuroblastoma (SH‐SY5Y) and glioblastoma (U‐87MG) coculture model is generated on HCGN with a specific cell‐to‐cell ratio (SH‐SY5Y: U‐87MG = 1:1), and their redox behaviors are successfully measured without destroying the distinct 3D structure of the multicellular spheroids. Using electrochemical signals as an indicator of spheroid viability, the effects of potential anticancer compounds on cocultured spheroids are further assessed. Remarkably, decreased cell viability in 3D spheroids caused by a low concentration of curcumin (30 µM) is detectable using the electrochemical method (29.4%) but not with a conventional colorimetric assay (CCK‐8). The detection is repeated more than ten times for both short‐ (63 h) and long‐term cultivation (144 h) without damaging the spheroids, enabling real‐time, non‐destructive pharmacokinetic analysis of various drug candidates. Therefore, it can be concluded that the hybrid platform is a highly promising, precise, and high‐throughput drug screening tool based on 3D cell cultivation. A multifunctional conductive platform that allows for highly efficient multicellular cancer spheroid formation and real‐time non‐destructive electrochemical monitoring of spheroid viability under various drug treatment conditions. The platform is useful for high throughput drug screening based on 3D multicellular culture models.