3D microengineered vascularized tumor spheroids for drug delivery and efficacy testing

Ahn, Jung Yong; Kim, Da-Hyun; Koo, Dong-Jun; Lim, Jae Yol; Lee, Jungseub; Ko, Jihoon; Kim, Seongchan; Kim, Minjae; Kang, Kyungsik; Min, Dal‐Hee; Kim, Sung-Yon; Kim, Yong Tae; Jeon, Noo Li

doi:10.1016/j.actbio.2022.10.009

Cited by 24 publications

(39 citation statements)

References 53 publications

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“…To partially overcome this limitation, the exploitation of 3D vascularized tumor spheroid-on-chip models could be an option. These models designate a microfluidic spheroid model, which moderately reflects the 3D architecture of the tumor, tumor heterogeneity, and microenvironment [ 111 , 112 , 113 ]. Unlike spheroids on their own, they are able to mimic the dynamic properties of the tumor microenvironment, for example, by ensuring the constant perfusion of cell medium (or any other relevant biological fluids) to supply nutrients, US contrast agents (e.g., MBs, nanobubbles, nanodroplets, etc.…”

Section: Future Perspectives and Conclusionmentioning

confidence: 99%

Tumor Spheroids as Model to Design Acoustically Mediated Drug Therapies: A Review

et al. 2023

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Tumor spheroids as well as multicellular tumor spheroids (MCTSs) are promising 3D in vitro tumor models for drug screening, drug design, drug targeting, drug toxicity, and validation of drug delivery methods. These models partly reflect the tridimensional architecture of tumors, their heterogeneity and their microenvironment, which can alter the intratumoral biodistribution, pharmacokinetics, and pharmacodynamics of drugs. The present review first focuses on current spheroid formation methods and then on in vitro investigations exploiting spheroids and MCTS for designing and validating acoustically mediated drug therapies. We discuss the limitations of the current studies and future perspectives. Various spheroid formation methods enable the easy and reproducible generation of spheroids and MCTSs. The development and assessment of acoustically mediated drug therapies have been mainly demonstrated in spheroids made up of tumor cells only. Despite the promising results obtained with these spheroids, the successful evaluation of these therapies will need to be addressed in more relevant 3D vascular MCTS models using MCTS-on-chip platforms. These MTCSs will be generated from patient-derived cancer cells and nontumor cells, such as fibroblasts, adipocytes, and immune cells.

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Section: Future Perspectives and Conclusionmentioning

confidence: 99%

Tumor Spheroids as Model to Design Acoustically Mediated Drug Therapies: A Review

et al. 2023

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“…For in vitro vasculature formation, generally seeded at a density between 5 to 10 million cells/mL, together with supporting cells. Fibroblasts are the most widely used cell stromal cells, although other cell types have also been used depending on the microenvironment to be mimicked (13)(14)(15)(16)(17)(18). The main reason for incorporating stromal cells is to support the formed microvasculature, which will otherwise regress after initial formation in the EC monoculture (19).…”

Section: Vasculogenesismentioning

confidence: 99%

“…Recently, quite a few groups have proposed introducing fibroblast and/or ECs to the tumor spheroid to improve vascularization, especially in the internal part of the tumor ( 17 , 30 – 32 ).…”

Section: Vascularization Strategiesmentioning

confidence: 99%

“…To better vascularize tumor spheroid, Ahn et al. ( 17 ) use a heterotypic spheroid that comprises HepG2 liver cancer cells and blood ECs. In the presence of intratumoral vessels, the tumor is found to have higher expression of genes associated with aggressive behavior in cancer, such as EMT, cell migration, cell proliferation, and vessel development.…”

Section: Vascularization Strategiesmentioning

confidence: 99%

“…To better vascularize tumor spheroids, Ahn et al. ( 17 ) used heterotypic spheroids comprising HepG2 liver cancer cells and blood ECs. They demonstrated that in the presence of intratumoral vessels, the tumor cells exhibited more aggressive metastasis.…”

Section: Therapeutic Screeningmentioning

confidence: 99%

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Recent advances in vascularized tumor-on-a-chip

Huang

2023

Front. Oncol.

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The vasculature plays a critical role in cancer progression and metastasis, representing a pivotal aspect in the creation of cancer models. In recent years, the emergence of organ-on-a-chip technology has proven to be a robust tool, capable of replicating in vivo conditions with exceptional spatiotemporal resolution, making it a significant asset in cancer research. This review delves into the latest developments in 3D microfluidic vascularized tumor models and their applications in vitro, focusing on heterotypic cellular interactions, the mechanisms of metastasis, and therapeutic screening. Additionally, the review examines the benefits and drawbacks of these models, as well as the future prospects for their advancement.

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An Overview of Advancements and Technologies in Vascularization Strategies for Tumor‐On‐A‐Chip Models

Parihar,

Sunildutt,

Rahim

et al. 2024

Advanced Therapeutics

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Vascularized tumor on a chip (VToC) entails emulating intricate microvascular networks like those observed in tumors through microfluidic devices, which are meticulously designed to offer a faithful representation of cancer in vitro, exploration of tumor biology, evaluation of drug efficacy, and anticipation of patient responses to therapies. Compared to conventional ones, VToC systems hold advantages by creating a milieu where physiological conditions for investigating tumor‐host interactions are pivotal in tumor advancement/therapy resilience. Nevertheless, VToC models confront limitations encompassing vascular network replication, biological fidelity, mechanical/chemical integrity, and intricacies of architectural design. Thus, drawbacks inherent to prevailing VToC models' intricacies, attributes, and vascular network establishment are imperative. This systematic review focuses on the recent advancements, technologies explored for incorporating VToC models, & vascularization approaches for investigation, and factors/parameters affecting complex tumor microenvironments in VToC models, along with the futuristic approach for the design strategies, fabrication techniques, understanding of vascular network, also VToC models with spheroid. A comprehensive analysis of VToC based on their limitations for a practical approach highlights the promising strategies for possible applications. This review will be essential regarding a complete overview of VToC models and the future direction toward developing efficient VToC models compared to the state‐of‐the‐art VToC.This article is protected by copyright. All rights reserved

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3D microengineered vascularized tumor spheroids for drug delivery and efficacy testing

Cited by 24 publications

References 53 publications

Tumor Spheroids as Model to Design Acoustically Mediated Drug Therapies: A Review

Tumor Spheroids as Model to Design Acoustically Mediated Drug Therapies: A Review

Recent advances in vascularized tumor-on-a-chip

An Overview of Advancements and Technologies in Vascularization Strategies for Tumor‐On‐A‐Chip Models

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