Organ-on-a-Chip Platforms for Drug Screening and Delivery in Tumor Cells: A Systematic Review
Abstract
:Simple Summary
Abstract
1. Introduction
2. Methods
2.1. Data Sources and Search Strategy
2.2. Validity Assessment
2.3. Inclusion and Exclusion Criteria
- Published in the last 10 years;
- The cell lines used corresponded to cancer cells;
- Use of microfluidic platforms or organs-on-chip in cancer studies;
- The 3D models allowed the performance of drug screening;
- Use of 3D cell culture models to test a new or standard cancer treatment.
3. Results and Discussion
3.1. Study Selection
3.2. Organ Models
3.2.1. Brain and Nervous System
3.2.2. Head and Neck
3.2.3. Bone
3.2.4. Lymphatic System
3.2.5. Angiogenesis
3.2.6. Colorectal
3.2.7. Pancreas
3.2.8. Liver
3.2.9. Kidney
3.2.10. Lung
3.2.11. Breast
3.2.12. Reproductive System
3.2.13. Multi-Organ Systems
3.3. Summary Results from 2D vs. 3D Culture Systems in Revision
4. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Organ/System | Features | Research Goal | Evaluated Drugs | Comparison Results between Cell Culture Systems | Representative Ref. |
---|---|---|---|---|---|
Brain and Nervous system | Mimic of BBB and glioblastoma microenvironment | NPs nanodelivery of cancer drug for glioblastoma treatment; validation of the OoC as a patient-specific cancer model | Antibody-functionalized nutlin-loaded nanostructured lipid carriers; chemoradiation using TMZ, CIS, O6BG and MX | Greater drug resistance in 2D cultures than in 3D cultures | [28,30] |
Bone | Microstructures for increased liquid mixing and cell-treatment interaction | Novel osteosarcoma treatment assessment;clinical drug validation | Fe77B10Si10C3 glass-coated amorphous magnetic microwires, MTX based treatments | Sedimentation of nanoparticles in traditional assays with static conditions lead to problems such as cell death being caused by undesired mechanisms | [33,34] |
Lymphatic System | Incorporation of different types of cells to mimic tumor microenvironment | Novel approach for creation of 3D tumor-stromal-immune cell spheroids | Lenalidomide | Cell death and reduction of proliferation higher in 2D cultures than in the 3D culture | [35] |
Angiogenesis | Hydrogel that leads to angiogenic sprouting patterns, pores to simulate capillaries, continuous fluid perfusion | Model validation for replication of tumor vasculature | Apatinib, vandetanib, linifanib, cabozantinib, cetuximab, bevacizumab | The effectiveness of some tested drugs was superior in 2D monolayer cultures while the opposite was noticed on others when compared to 3D cultures.Vasculature is not mimicked in 2D cultures | [37,43] |
Pancreas | Culture of cells with different phenotypes to mimic tumor microenvironment and intra-tumoral heterogeneity; endothelium-mimicking membrane | Pancreatic ductal adenocarcinoma model validation for drug evaluation | GEM | IC50 and EC50 values of tested drugs were higher for the 3D culture than for the 2D culture | [52,53] |
Lung | Layers separated by porous membrane to simulate blood–air interface | Lung cancer model validation for real-time drug effect evaluation | DOX and docetaxel, gefitinib | More cells were affected by therapeutic drug in 3D static culture than in 3D dynamic culture or 2D static and dynamic cultures | [59,62] |
Breast | Microchannels separated by a thin ECM-derived membrane to replicate the human mammary duct | Evaluation of specific cellular signaling; breast ductal carcinoma model validation for drug evaluation | Tocilizumab, reparixin, UK-356618, PTX | Cytotoxic effects of therapeutic drugs greater on the 2D culture than on the 3D culture | [76,79] |
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Gonçalves, I.M.; Carvalho, V.; Rodrigues, R.O.; Pinho, D.; Teixeira, S.F.C.F.; Moita, A.; Hori, T.; Kaji, H.; Lima, R.; Minas, G. Organ-on-a-Chip Platforms for Drug Screening and Delivery in Tumor Cells: A Systematic Review. Cancers 2022, 14, 935. https://doi.org/10.3390/cancers14040935
Gonçalves IM, Carvalho V, Rodrigues RO, Pinho D, Teixeira SFCF, Moita A, Hori T, Kaji H, Lima R, Minas G. Organ-on-a-Chip Platforms for Drug Screening and Delivery in Tumor Cells: A Systematic Review. Cancers. 2022; 14(4):935. https://doi.org/10.3390/cancers14040935
Chicago/Turabian StyleGonçalves, Inês M., Violeta Carvalho, Raquel O. Rodrigues, Diana Pinho, Senhorinha F. C. F. Teixeira, Ana Moita, Takeshi Hori, Hirokazu Kaji, Rui Lima, and Graça Minas. 2022. "Organ-on-a-Chip Platforms for Drug Screening and Delivery in Tumor Cells: A Systematic Review" Cancers 14, no. 4: 935. https://doi.org/10.3390/cancers14040935