Article

Opportunities and challenges for use of tumor spheroids as models to test drug delivery and efficacy

Department of Periodontics & Oral Medicine, University of Michigan School of Dentistry, The University of Michigan, Ann Arbor, MI 48109-2099, United States.
Journal of Controlled Release (Impact Factor: 7.26). 05/2012; 164(2). DOI: 10.1016/j.jconrel.2012.04.045
Source: PubMed

ABSTRACT 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 models 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. By addressing these challenges with possible solutions, multicellular spheroids are becoming an increasingly useful in vitro tool for drug screening and delivery to pathological tissues and organs.

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    • "Often, promising results obtained from 2D cannot be translated similarly into in vivo settings (Goodman et al., 2008). Whereas cells on 2D are exposed to a uniform environment with sufficient oxygen and nutrients, cells in solid tumors are exposed to gradients of critical chemical and biological signals (Mehta et al., 2012), which can exert both stimulatory and inhibitory effects on tumor progression (Mehta et al., 2012). Intriguingly, certain tumor cells from cancer patients are intrinsically resistant to a broad spectrum of chemotherapeutic drugs without any previous exposure to those cytotoxic agents (Sanchez et al., 2009; Zhu et al., 2005, 2012). "
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    • "The main advantages of the MTS are their simple spherical symmetry and the fact that they can be produced in large quantities. These characteristics make them popular both in mathematical modeling and in biological research: MTS provide an experimental biological model that has allowed researchers to determine protein expression McMahon et al. (2012); Gupta and Johansson (2012), check mathematical models Radszuweit et al. (2009); Bertuzzi et al. (2010); Kazmi et al. (2012), and study drug delivery to treat cancer disease Mehta et al. (2012); Gibot et al. (2013), to mention a few applications. The understanding of how MTS grow is indeed crucial to further comprehend some aspects of in vivo tumor progression. "
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