Blanco-Fernandez Barbara, Gaspar Vítor M, Engel Elisabeth, Mano João F
Department of Chemistry, CICECO - Aveiro Institute of Materials, University of Aveiro Campus Universitário de Santiago Aveiro 3810-193 Portugal.
Institute for Bioengineering of Catalonia (IBEC) The Barcelona Institute of Science and Technology Baldiri Reixac 10-12 Barcelona 08028 Spain.
Adv Sci (Weinh). 2021 Jan 4;8(4):2003129. doi: 10.1002/advs.202003129. eCollection 2021 Feb.
The establishment of tumor microenvironment using biomimetic in vitro models that recapitulate key tumor hallmarks including the tumor supporting extracellular matrix (ECM) is in high demand for accelerating the discovery and preclinical validation of more effective anticancer therapeutics. To date, ECM-mimetic hydrogels have been widely explored for 3D in vitro disease modeling owing to their bioactive properties that can be further adapted to the biochemical and biophysical properties of native tumors. Gathering on this momentum, herein the current landscape of intrinsically bioactive protein and peptide hydrogels that have been employed for 3D tumor modeling are discussed. Initially, the importance of recreating such microenvironment and the main considerations for generating ECM-mimetic 3D hydrogel in vitro tumor models are showcased. A comprehensive discussion focusing protein, peptide, or hybrid ECM-mimetic platforms employed for modeling cancer cells/stroma cross-talk and for the preclinical evaluation of candidate anticancer therapies is also provided. Further development of tumor-tunable, proteinaceous or peptide 3D microtesting platforms with microenvironment-specific biophysical and biomolecular cues will contribute to better mimic the in vivo scenario, and improve the predictability of preclinical screening of generalized or personalized therapeutics.
利用仿生体外模型建立肿瘤微环境，该模型可重现包括肿瘤支持性细胞外基质（ECM）在内的关键肿瘤特征，对于加速发现更有效的抗癌疗法并进行临床前验证的需求很高。迄今为止，由于其具有生物活性特性，可进一步适应天然肿瘤的生化和生物物理特性，ECM模拟水凝胶已被广泛用于三维体外疾病建模。基于这一趋势，本文讨论了已用于三维肿瘤建模的具有内在生物活性的蛋白质和肽水凝胶的现状。首先，展示了重建这种微环境的重要性以及在体外肿瘤模型中生成ECM模拟三维水凝胶的主要考虑因素。还提供了一个全面的讨论，重点是用于模拟癌细胞/基质相互作用以及用于候选抗癌疗法临床前评估的蛋白质、肽或混合ECM模拟平台。进一步开发具有微环境特异性生物物理和生物分子线索的肿瘤可调、蛋白质或肽三维微测试平台，将有助于更好地模拟体内情况，并提高对通用或个性化疗法临床前筛选的可预测性。
