Self-Assembled Peptide Habitats to Model Tumor Metastasis

Abstract

Metastatic tumours are complex ecosystems; a community of multiple cell types, including cancerous cells, fibroblasts, and immune cells that exist within a supportive and specific microenvironment. The interplay of these cells, together with tissue specific chemical, structural and temporal signals within a three-dimensional (3D) habitat, direct tumour cell behavior, a subtlety that can be easily lost in 2D tissue culture. Here, we investigate a significantly improved tool, consisting of a novel matrix of functionally programmed peptide sequences, self-assembled into a scaffold to enable the growth and the migration of multicellular lung tumour spheroids, as proof-of-concept. This 3D functional model aims to mimic the biological, chemical, and contextual cues of an in vivo tumor more closely than a typically used, unstructured hydrogel, allowing spatial and temporal activity modelling. This approach shows promise as a cancer model, enhancing current understandings of how tumours progress and spread over time within their microenvironment.

Simple Complexity: Incorporating Bioinspired Delivery Machinery within Self-Assembled Peptide Biogels

“…This typically entails loading drugs onto (nano)particles [ 14 ], encapsulating in vesicles [ 15 ], reversibly attaching to polymers [ 16 ], or using bulk hydrogels to immobilize the drug via steric hinderance [ 17 ]. Hydrogels are typically considered to be networks consisting of a structure that encapsulates a significant amount of water [ 18 ]. This hydrated nature enables water-soluble fractions to be loaded into the system or added to structures that can be embedded.…”

“…An amphiphilic peptide dendrimer (AmPD), which assembled into nano-carriers for effective encapsulation DOX, improved the intracellular uptake and accumulation of DOX in drug-resistant breast cancer cells and improved permeation in 3D multicellular tumor spheroids compared with free DOX [ 61 ]. SAP hydrogels can be employed as model systems to assess the effectiveness of drugs in a more tissue mimetic 3D environment than the traditional 2D systems, enabling the modeling of metastasis and the utility of embedded drugs [ 18 ], as well as studying the chemotaxis of antitumor T cells in response to cytokine gradients [ 98 ]. Bai et al developed an amphiphilic SAP allowing for the encapsulation of DOX in a neutral medium.…”