通过多酚膜涂层调节树突状细胞免疫。
Dendritic Cell Immune Modulation via Polyphenol Membrane Coatings.
发表日期:2024 May 23
作者:
Morgan E Janes, Kyung Soo Park, Alexander P Gottlieb, Alexander Curreri, Kolade Adebowale, Jayoung Kim, Samir Mitragotri
来源:
PHYSICAL THERAPY & REHABILITATION JOURNAL
摘要:
细胞搭便车是一种新兴的体内控制过继转移免疫细胞的策略。搭便车方法主要是通过纳米和微粒粘附到细胞膜上介导的,这具有通过局部药物输送调节转移细胞的能力。尽管采用这种策略的 T 细胞疗法已进入临床,但包括树突状细胞 (DC) 在内的吞噬细胞的工程设计更具挑战性。 DC 疫苗对一系列疾病具有巨大的潜力,联合给药是操纵其功能和克服体内可塑性的一种有吸引力的策略。然而,由于 DC 具有广泛的吞噬能力,因此与当前的搭便车方法不兼容。在这项工作中,我们开发并验证了 META(使用单宁酸的膜工程),首次实现了 DC 细胞的搭便车。 META 采用多酚单宁酸 (TA) 促进蛋白质药物货物在细胞膜上的超分子组装,从而能够创建细胞表面结合制剂,用于将药物局部递送至载体 DC。我们优化了 META 配方,以单独和组合地掺入和释放具有不同物理特性的蛋白质货物,并保持 DC 活力和迁移等关键功能。我们进一步表明,装载促炎或抗炎货物的 META 可以影响载体细胞表型,从而证明该方法在从癌症到自身免疫性疾病的应用中的灵活性。总的来说,这种方法展示了一个局部控制吞噬免疫细胞的新平台,作为临床上推进 DC 疗法的下一步。
Cellular hitchhiking is an emerging strategy for the in vivo control of adoptively transferred immune cells. Hitchhiking approaches are primarily mediated by adhesion of nano and microparticles to the cell membrane, which conveys an ability to modulate transferred cells via local drug delivery. Although T cell therapies employing this strategy have progressed into the clinic, phagocytic cells including dendritic cells (DCs) are much more challenging to engineer. DC vaccines hold great potential for a spectrum of diseases, and the combination drug delivery is an attractive strategy to manipulate their function and overcome in vivo plasticity. However, DCs are not compatible with current hitchhiking approaches due to their broad phagocytic capacity. In this work, we developed and validated META (membrane engineering using tannic acid) to enable DC cellular hitchhiking for the first time. META employs the polyphenol tannic acid (TA) to facilitate supramolecular assembly of protein drug cargoes on the cell membrane, enabling the creation of cell surface-bound formulations for local drug delivery to carrier DCs. We optimized META formulations to incorporate and release protein cargoes with varying physical properties alone and in combination and to preserve DC viability and critical functions such as migration. We further show that META loaded with either a pro- or anti-inflammatory cargo can influence the carrier cell phenotype, thus demonstrating the flexibility of the approach for applications from cancer to autoimmune disease. Overall, this approach illustrates a new platform for the local control of phagocytic immune cells as a next step to advance DC therapies in the clinic.