Department of Chemical and Biomolecular Engineering, The Institute for NanoBioTechnology Physical-Sciences Oncology Center, Johns Hopkins University, Baltimore, MD 21218, USA.
Department of Chemical and Biomolecular Engineering, The Institute for NanoBioTechnology Physical-Sciences Oncology Center, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Adv Drug Deliv Rev. 2019 Sep-Oct;149-150:95-106. doi: 10.1016/j.addr.2019.08.005. Epub 2019 Aug 14.
In recent years, as the mechanisms of vasculogenesis and angiogenesis have been uncovered, the functions of various pro-angiogenic growth factors (GFs) and cytokines have been identified. Therefore, therapeutic angiogenesis, by delivery of GFs, has been sought as a treatment for many vascular diseases. However, direct injection of these protein drugs has proven to have limited clinical success due to their short half-lives and systemic off-target effects. To overcome this, hydrogel carriers have been developed to conjugate single or multiple GFs with controllable, sustained, and localized delivery. However, these attempts have failed to account for the temporal complexity of natural angiogenic pathways, resulting in limited therapeutic effects. Recently, the emerging ideas of optimal sequential delivery of multiple GFs have been suggested to better mimic the biological processes and to enhance therapeutic angiogenesis. Incorporating sequential release into drug delivery platforms will likely promote the formation of neovasculature and generate vast therapeutic potential.
近年来，随着血管发生和血管生成机制的揭示，各种促血管生成生长因子（GFs）和细胞因子的功能已被确定。因此，通过递送 GFs 来实现治疗性血管生成，已被寻求作为许多血管疾病的治疗方法。然而，由于这些蛋白质药物的半衰期短和全身脱靶效应，直接注射这些药物已被证明临床效果有限。为了克服这一问题，已经开发了水凝胶载体来将单个或多个 GFs 与可控、持续和局部递送相结合。然而，这些尝试未能考虑到天然血管生成途径的时间复杂性，导致治疗效果有限。最近，有人提出了最佳顺序递多种 GFs 的新想法，以更好地模拟生物过程并增强治疗性血管生成。将顺序释放纳入药物递送平台可能会促进新血管的形成并产生巨大的治疗潜力。
