The lack of in vitro models that represent the native tumor microenvironment is a significant challenge for cancer research. Two-dimensional (2D) monolayer culture has long been the standard for in vitro cell-based studies. However, differences between 2D culture and the in vivo environment have led to poor translation of cancer research from in vitro to in vivo models, slowing the progress of the field. Recent advances in three-dimensional (3D) culture have improved the ability of in vitro culture to replicate in vivo conditions. Although 3D cultures still cannot achieve the complexity of the in vivo environment, they can still better replicate the cell–cell and cell–matrix interactions of solid tumors. Multicellular tumor spheroids (MCTS) are three-dimensional (3D) clusters of cells with tumor-like features such as oxygen gradients and drug resistance, and represent an important translational tool for cancer research. Accordingly, natural and synthetic polymers, including collagen, hyaluronic acid, Matrigel®, polyethylene glycol (PEG), alginate and chitosan, have been used to form and study MCTS for improved clinical translatability. This review evaluates the current state of biomaterial-based MCTS formation, including advantages and disadvantages of the different biomaterials and their recent applications to the field of cancer research, with a focus on the past five years.

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Peptides play an essential role in biotechnological applications as therapeutic and diagnostic agents due to their tunable activity for desired function. So far, a variety of peptide therapeutics and their peptide-based carriers have been engineered for drug delivery applications. However, in order to design and develop such systems for tissue-specific applications, the cellular microenvironment must be properly considered. Peptide-based materials have vast potential applications, particularly for cancer-related systems. Thus, in this chapter, we first focus on different design strategies and considerations for drug-release mechanisms in peptide-based materials. Then, we explain how tumor microenvironments may be distinguished from healthy tissue, including discussion of tumor-specific drug delivery strategies. Finally, the growing significance of peptide chemotherapeutics will be emphasized in terms of design concerns and current applications.