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Advancements in the Metabolic Profiling of Three-Dimensional Brain Tumor Spheroids for Drug Screening
Published on: September 5, 2025
A novel 96-well multielectrode array based impedimetric monitoring platform for comparative drug efficacy analysis on
Marie Eichler1, Heinz-Georg Jahnke1, Dana Krinke1
1Center for Biotechnology and Biomedicine (BBZ), University of Leipzig, Division of Molecular Biological-Biochemical Processing Technology, Deutscher Platz 5, 04103 Leipzig, Germany.
Abstract:
Aggressive cancer entities like neuroblastoma and glioblastoma multiforme are still difficult to treat and have discouraging prognosis in malignant stage. Since each tumor has its own characteristics concerning the sensitivity towards different chemotherapeutics and moreover, can obtain resistance, the development of novel chemotherapeutics with a broad activity spectrum, high efficacy and minimum side effects is a continuous process. Sophisticated in vitro assays for comprehensive prediction of in vivo drug efficacy and side effects represent an actual bottleneck in the drug development process. In this context, we developed a novel in vitro 2D and 3D multiwell-multielectrode device for drug efficacy monitoring based on direct real-time impedance spectroscopy measurement in combination with our unique 96-well multielectrode arrays and microcavity arrays. For demonstration, we used three neuro- and glioblastoma cell lines that were cultured as monolayer and multicellular tumor spheroids for recapitulating in vivo conditions. Using our novel 96-well multielectrode array based system it was possible to detect time and concentration dependent responses concerning treatment with doxorubicin, etoposide and vincristine. While all tested chemotherapeutics revealed high potency for apoptosis induction in neuroblastoma cells, etoposide was ineffective for glioblastoma cell lines. Determination of IC50 values allowed us to compare drug efficacy in 2D and 3D culture models and moreover, revealed chemotherapeutic and tumor cell line specific activity patterns. These pharmacokinetic patterns are of great interest in the context of preclinical drug development. Thus, impedance spectroscopy based monitoring systems could be used for the fast in vitro based in vivo prediction of novel anti-tumor drugs.
Insights
A new 96-well multielectrode array system uses impedance spectroscopy for real-time monitoring of anti-cancer drug efficacy. This novel device aids in predicting drug effectiveness and identifying treatment resistance in neuroblastoma and glioblastoma models.
Area of Science:
- Biomedical Engineering
- Oncology
- Drug Development
Background:
- Aggressive cancers like neuroblastoma and glioblastoma multiforme present treatment challenges with poor prognoses.
- Tumor-specific drug sensitivity and acquired resistance necessitate the development of novel chemotherapeutics with broad efficacy and minimal side effects.
- Accurate in vitro assays for predicting in vivo drug efficacy and side effects are crucial but currently limited.
Purpose of the Study:
- To develop and validate a novel in vitro 2D and 3D multiwell-multielectrode device for real-time drug efficacy monitoring.
- To assess the system's capability in predicting the efficacy of standard chemotherapeutics against neuroblastoma and glioblastoma cell lines.
- To compare drug responses in 2D and 3D cell culture models for improved preclinical drug development.
Main Methods:
- Development of a novel in vitro 2D and 3D multiwell-multielectrode device utilizing 96-well multielectrode and microcavity arrays.
- Real-time impedance spectroscopy for direct monitoring of drug-induced cellular responses.
- Culturing of three neuroblastoma and glioblastoma cell lines as both monolayers (2D) and multicellular tumor spheroids (3D).
- Treatment with doxorubicin, etoposide, and vincristine to evaluate drug efficacy and determine IC50 values.
Main Results:
- The system successfully detected time- and concentration-dependent responses to doxorubicin, etoposide, and vincristine.
- All tested chemotherapeutics showed high apoptosis induction in neuroblastoma cells, while etoposide was ineffective against glioblastoma.
- Comparison of IC50 values in 2D and 3D models revealed distinct chemotherapeutic and tumor cell line-specific activity patterns.
- Identified pharmacokinetic patterns are valuable for preclinical drug development.
Conclusions:
- The novel impedance spectroscopy-based monitoring system enables rapid in vitro assessment of anti-cancer drug efficacy.
- This system facilitates the prediction of in vivo drug performance, aiding in the development of novel anti-tumor agents.
- The ability to differentiate drug responses in 2D vs. 3D models enhances the predictive power for preclinical drug screening.
