Hwang Jeongmin, Sullivan Millicent O, Kiick Kristi L
Department of Biomedical Engineering, University of Delaware, Newark, DE, United States.
Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE, United States.
Front Bioeng Biotechnol. 2020 Feb 18;8:69. doi: 10.3389/fbioe.2020.00069. eCollection 2020.
The use of drug delivery vehicles to improve the efficacy of drugs and to target their action at effective concentrations over desired periods of time has been an active topic of research and clinical investigation for decades. Both synthetic and natural drug delivery materials have facilitated locally controlled as well as targeted drug delivery. Extracellular matrix (ECM) molecules have generated widespread interest as drug delivery materials owing to the various biological functions of ECM. Hydrogels created using ECM molecules can provide not only biochemical and structural support to cells, but also spatial and temporal control over the release of therapeutic agents, including small molecules, biomacromolecules, and cells. In addition, the modification of drug delivery carriers with ECM fragments used as cell-binding ligands has facilitated cell-targeted delivery and improved the therapeutic efficiency of drugs through interaction with highly expressed cellular receptors for ECM. The combination of ECM-derived hydrogels and ECM-derived ligand approaches shows synergistic effects, leading to a great promise for the delivery of intracellular drugs, which require specific endocytic pathways for maximal effectiveness. In this review, we provide an overview of cellular receptors that interact with ECM molecules and discuss examples of selected ECM components that have been applied for drug delivery in both local and systemic platforms. Finally, we highlight the potential impacts of utilizing the interaction between ECM components and cellular receptors for intracellular delivery, particularly in tissue regeneration applications.
几十年来，使用药物递送载体来提高药物疗效并在期望的时间段内将其作用靶向于有效浓度一直是研究和临床研究的一个活跃主题。合成和天然药物递送材料都促进了局部控制以及靶向药物递送。由于细胞外基质（ECM）的各种生物学功能，ECM分子作为药物递送材料引起了广泛关注。使用ECM分子制备的水凝胶不仅可以为细胞提供生化和结构支持，还可以对包括小分子、生物大分子和细胞在内的治疗剂的释放进行空间和时间控制。此外，用作为细胞结合配体的ECM片段修饰药物递送载体有助于细胞靶向递送，并通过与ECM的高表达细胞受体相互作用提高药物的治疗效率。源自ECM的水凝胶和源自ECM的配体方法的结合显示出协同效应，为细胞内药物递送带来了巨大希望，而细胞内药物递送需要特定的内吞途径才能达到最大效果。在本综述中，我们概述了与ECM分子相互作用的细胞受体，并讨论了在局部和全身平台上已应用于药物递送的选定ECM成分的实例。最后，我们强调了利用ECM成分与细胞受体之间的相互作用进行细胞内递送的潜在影响，特别是在组织再生应用中。
