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Hydrogel Arrays Enable Increased Throughput for Screening Effects of Matrix Components and Therapeutics in 3D Tumor Models
Published on: June 16, 2022
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Quantifying nanotherapeutic penetration using a hydrogel-based microsystem as a new 3D in vitro platform
Saba Goodarzi1, Audrey Prunet1, Fabien Rossetti1
1University of Lyon, Université Claude Bernard Lyon 1, CNRS, Institut Lumière Matière, F-69622, Villeurbanne, France. charlotte.riviere@univ-lyon1.fr.
Lab on a Chip
|June 10, 2021
Summary
A novel, user-friendly 3D microsystem using agarose microwells enables reproducible formation of multi-cellular tumor spheroids for nanotherapeutic studies. This 3D model reveals distinct nanoparticle behavior compared to 2D assays, improving in vitro drug screening predictability.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Traditional 2D cell cultures inadequately mimic the 3D tumor microenvironment, limiting nanotherapeutic efficacy predictions.
- Existing 3D multi-cellular tumor spheroid (MCTS) models face challenges like low yield, slow production, and manipulation difficulties.
- Current spheroid-on-chip systems often demand specialized microfluidics expertise, hindering accessibility for cell biology labs.
Purpose of the Study:
- To develop a simple, flexible, and user-friendly 3D in vitro microsystem for generating reproducible MCTS.
- To evaluate the transport kinetics and intracellular localization of ultrasmall nanoparticles (AGuIX®) within colorectal cancer MCTS.
- To compare nanotherapeutic behavior in the developed 3D model versus traditional 2D assays.
Main Methods:
- Fabrication of an agarose-based microwell system compatible with multi-well plates for high-throughput MCTS formation.
- In situ imaging of nanoparticle (AGuIX®) distribution and kinetics within MCTS using confocal microscopy.
- Comparative analysis of nanoparticle uptake and localization in both 2D cultures and the 3D MCTS model.
Main Results:
- The agarose microwell system enabled rapid, reproducible formation of hundreds of MCTS via simple pipetting.
- Significant differences in AGuIX® nanoparticle accumulation were observed between 2D and 3D models.
- AGuIX® nanoparticles were found intracellularly within MCTS, primarily in lysosomes and occasionally in mitochondria, with extracellular components clearing over time.
Conclusions:
- The developed agarose-based microsystem provides a user-friendly and flexible 3D platform for MCTS generation and nanotherapeutic evaluation.
- This 3D model offers improved in vitro prediction of nanotherapeutic behavior compared to 2D assays.
- The platform facilitates detailed spatial and temporal analysis of nanotherapeutic penetration and distribution within tumor spheroids.
