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Updated: Jul 20, 2025
Generation of 3D Tumor Spheroids for Drug Evaluation Studies
Published on: February 24, 2023
Heterotypic tumor spheroids: a platform for nanomedicine evaluation
Faezeh Vakhshiteh1, Zeinab Bagheri2, Marziye Soleimani3
1Oncopathology Research Center, Iran University of Medical Sciences (IUMS), Tehran, Iran.
Abstract:
Nanomedicine has emerged as a promising therapeutic approach, but its translation to the clinic has been hindered by the lack of cellular models to anticipate how tumor cells will respond to therapy. Three-dimensional (3D) cell culture models are thought to more accurately recapitulate key features of primary tumors than two-dimensional (2D) cultures. Heterotypic 3D tumor spheroids, composed of multiple cell types, have become more popular than homotypic spheroids, which consist of a single cell type, as a superior model for mimicking in vivo tumor heterogeneity and physiology. The stromal interactions demonstrated in heterotypic 3D tumor spheroids can affect various aspects, including response to therapy, cancer progression, nanomedicine penetration, and drug resistance. Accordingly, to design more effective anticancer nanomedicinal therapeutics, not only tumor cells but also stromal cells (e.g., fibroblasts and immune cells) should be considered to create a more physiologically relevant in vivo microenvironment. This review aims to demonstrate current knowledge of heterotypic 3D tumor spheroids in cancer research, to illustrate current advances in utilizing these tumor models as a novel and versatile platform for in vitro evaluation of nanomedicine-based therapeutics in cancer research, and to discuss challenges, guidelines, and future directions in this field.
Insights
Heterotypic three-dimensional (3D) tumor spheroids, incorporating stromal cells, offer a superior model for predicting nanomedicine efficacy in cancer research. These advanced models better mimic tumor microenvironments than traditional 2D cultures.
Area of Science:
- Oncology
- Biomedical Engineering
- Nanotechnology
Background:
- Nanomedicine shows promise for cancer therapy, but clinical translation is limited by inadequate preclinical models.
- Traditional two-dimensional (2D) cell cultures fail to replicate the complex tumor microenvironment.
- Three-dimensional (3D) cell culture models, particularly heterotypic spheroids, offer a more accurate representation of in vivo tumor physiology and heterogeneity.
Purpose of the Study:
- To review the current knowledge and applications of heterotypic 3D tumor spheroids in cancer research.
- To highlight the utility of these models for in vitro evaluation of nanomedicine-based therapeutics.
- To discuss challenges and future directions for using 3D spheroids in nanomedicine development.
Main Methods:
- Review of existing literature on 3D cell culture, tumor microenvironments, and nanomedicine.
- Analysis of studies utilizing heterotypic 3D tumor spheroids for cancer research.
- Synthesis of findings on the impact of stromal interactions in 3D models on therapeutic response.
Main Results:
- Heterotypic 3D tumor spheroids, including fibroblasts and immune cells, better mimic in vivo tumor heterogeneity and stromal interactions.
- These models demonstrate significant effects on nanomedicine penetration, drug resistance, and overall therapeutic response.
- Stromal interactions within 3D spheroids are crucial for accurately predicting treatment outcomes.
Conclusions:
- Heterotypic 3D tumor spheroids provide a more physiologically relevant platform for evaluating nanomedicine efficacy compared to 2D cultures.
- Incorporating stromal cells into 3D models is essential for designing effective anticancer nanomedicinal therapeutics.
- Further research and standardization of 3D spheroid models are needed to advance nanomedicine development for cancer treatment.
