Opportunities and Challenges for use of Tumor Spheroids as Models to Test Drug Delivery and Efficacy

By G. Mehta, A. Hsiao, Marylou Ingram, G. Luker, Shuichi Takayama. Journal of Controlled Release, 2012

1,100 citations recorded by the source corpus.

Multicellular spheroids are three dimensional in vitro microscale tissue analogs. The current article examines the suitability of spheroids as an in vitro platform for testing drug delivery systems. Spheroids model critical physiologic parameters present in vivo, including complex multicellular architecture, barriers to mass transport, and extracellular matrix deposition. Relative to two-dimensional cultures, spheroids also provide better target cells for drug testing and are appropriate in vitro model for studies of drug penetration. Key challenges associated with creation of uniformly sized spheroids, spheroids with small number of cells and co-culture spheroids are emphasized in the article. Moreover, the assay techniques required for the characterization of drug delivery and efficacy in spheroids and the challenges associated with such studies are discussed. Examples for the use of spheroids in drug delivery and testing are also emphasized. With these challenges and the possible solutions, multicellular spheroids are becoming an increasingly useful in vitro tool for drug screening and delivery to pathological tissues and organs.

Subfields: Biomedical Engineering, Cell Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/0eafd835ebff7d4f8935225a6306a080cba39515

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In Biomedical Engineering

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Citations in the corpus

• Three-Dimensional Cell Culture Systems and Their Applications in Drug Discovery and Cell-Based Biosensors (2014, background): “The core cells receive less oxygen, growth factors, and nutrients from the medium, and tend to be in a quiescent or hypoxic state.(26) Such cellular heterogeneity is very similar to in vivo tissues, particularly in tumors.”
• Spheroids-on-a-chip: Recent advances and design considerations in microfluidic platforms for spheroid formation and culture (2018, background): “The compactness of spheroids endows them with several features analogous to those of in-vivo tumor tissues [3].”
• Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer (2021, background): “Aggregate culture platforms of particular interest are scaffold‐free systems, also referred to as spheroids or organoids, in which heterogeneous populations can be evaluated for drug resistance and sensitivity or can be used to establish hypoxic cancer models.(72,75,76) However, organoids commonly c”
• In Vitro Tumor Models: Advantages, Disadvantages, Variables, and Selecting the Right Platform (2016, methodology): “Overall, MCTS are more resistant to treatment than cells in 2D culture (Lin and Chang, 2008; Mehta et al., 2012; Fennema et al., 2013) and can recapitulate the drug resistance observed in solid tumors (Friedrich et al.”