Related Experiment Video
Updated: Jul 6, 2025
Generation of 3D Tumor Spheroids for Drug Evaluation Studies
Published on: February 24, 2023
Delivery of Anticancer Drugs Using Microbubble-Assisted Ultrasound in a 3D Spheroid Model
Marie Roy1, Corentin Alix1, Julien Burlaud-Gaillard2
1UMR 1253, iBrain, Université de Tours, Inserm, 37032 Tours, France.
Abstract:
Tumor spheroids are promising three-dimensional (3D) in vitro tumor models for the evaluation of drug delivery methods. The design of noninvasive and targeted drug methods is required to improve the intratumoral bioavailability of chemotherapeutic drugs and reduce their adverse off-target effects. Among such methods, microbubble-assisted ultrasound (MB-assisted US) is an innovative modality for noninvasive targeted drug delivery. The aim of the present study is to evaluate the efficacy of this US modality for the delivery of bleomycin, doxorubicin, and irinotecan in colorectal cancer (CRC) spheroids. MB-assisted US permeabilized the CRC spheroids to propidium iodide, which was used as a drug model without affecting their growth and viability. Histological analysis and electron microscopy revealed that MB-assisted US affected only the peripheral layer of the CRC spheroids. The acoustically mediated bleomycin delivery induced a significant decrease in CRC spheroid growth in comparison to spheroids treated with bleomycin alone. However, this US modality did not improve the therapeutic efficacy of doxorubicin and irinotecan on CRC spheroids. In conclusion, this study demonstrates that tumor spheroids are a relevant approach to evaluate the efficacy of MB-assisted US for the delivery of chemotherapeutics.
Insights
Microbubble-assisted ultrasound (MB-assisted US) enhances chemotherapy delivery in colorectal cancer (CRC) spheroids. While effective for bleomycin, this method did not improve doxorubicin or irinotecan efficacy in these 3D tumor models.
Area of Science:
- Oncology
- Drug Delivery Systems
- Biotechnology
Background:
- Three-dimensional (3D) tumor spheroids are valuable *in vitro* models for assessing drug delivery.
- Noninvasive, targeted drug delivery methods are crucial for improving intratumoral drug bioavailability and reducing side effects.
- Microbubble-assisted ultrasound (MB-assisted US) presents an innovative approach for noninvasive, targeted drug delivery.
Purpose of the Study:
- To evaluate the efficacy of MB-assisted US for delivering bleomycin, doxorubicin, and irinotecan in colorectal cancer (CRC) spheroids.
- To assess the impact of MB-assisted US on CRC spheroid permeability, growth, and viability.
Main Methods:
- Utilized 3D CRC spheroids as an *in vitro* tumor model.
- Employed MB-assisted US to facilitate the delivery of chemotherapeutic agents (bleomycin, doxorubicin, irinotecan).
- Assessed spheroid permeability using propidium iodide as a drug model.
- Conducted histological analysis and electron microscopy to evaluate treatment effects.
Main Results:
- MB-assisted US increased CRC spheroid permeability to propidium iodide without compromising spheroid growth or viability.
- Histological and electron microscopy analyses indicated that MB-assisted US primarily affected the peripheral layer of the spheroids.
- Acoustically mediated bleomycin delivery significantly reduced CRC spheroid growth compared to bleomycin treatment alone.
- MB-assisted US did not enhance the therapeutic efficacy of doxorubicin or irinotecan in the CRC spheroids.
Conclusions:
- Tumor spheroids serve as a relevant and effective model for evaluating the efficacy of MB-assisted US in chemotherapeutic drug delivery.
- MB-assisted US shows promise for targeted delivery of specific chemotherapeutics like bleomycin in 3D cancer models.
- Further research is needed to optimize MB-assisted US parameters for enhancing the delivery of other chemotherapeutic agents.
