Sloand Janna N, Nguyen Theodore T, Zinck Scott A, Cook Erik C, Zimudzi Tawanda J, Showalter Scott A, Glick Adam B, Simon Julianna C, Medina Scott H
Department of Biomedical Engineering, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.
Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.
ACS Nano. 2020 Apr 28;14(4):4061-4073. doi: 10.1021/acsnano.9b08745. Epub 2020 Mar 11.
The inability to spatiotemporally guide proteins in tissues and efficiently deliver them into cells remains a key barrier to realizing their full potential in precision medicine. Here, we report ultrasound-sensitive fluoro-protein nanoemulsions which can be acoustically tracked, guided, and activated for on-demand cytosolic delivery of proteins, including antibodies, using clinically relevant diagnostic ultrasound. This advance is accessed through the discovery of a family of fluorous tags, or FTags, that transiently mask proteins to mediate their efficient dispersion into ultrasound-sensitive liquid perfluorocarbons, a phenomenon akin to dissolving an egg in liquid Teflon. We identify the biochemical basis for protein fluorous masking and confirm FTag coatings are shed during delivery, without disrupting the protein structure or function. Harnessing the ultrasound sensitivity of fluorous emulsions, real-time imaging is used to simultaneously monitor and activate FTag-protein complexes to enable controlled cytosolic antibody delivery and . These findings may advance the development of image-guided, protein-based biosensing and therapeutic modalities.
在组织中对蛋白质进行时空引导并有效地将其递送至细胞内的能力不足，仍然是蛋白质在精准医学中充分发挥其潜力的关键障碍。在此，我们报道了一种对超声敏感的荧光蛋白纳米乳液，它可以通过临床相关的诊断超声进行声学追踪、引导和激活，从而按需将包括抗体在内的蛋白质递送至细胞质中。这一进展是通过发现一类氟标签（FTags）实现的，这些氟标签可短暂地掩盖蛋白质，介导其有效地分散到对超声敏感的液态全氟化碳中，这一现象类似于将鸡蛋溶解在液态聚四氟乙烯中。我们确定了蛋白质氟掩蔽的生化基础，并证实FTag涂层在递送过程中脱落，而不会破坏蛋白质的结构或功能。利用氟乳液的超声敏感性，实时成像用于同时监测和激活FTag-蛋白质复合物，以实现可控的细胞质抗体递送。这些发现可能会推动基于蛋白质的图像引导生物传感和治疗方式的发展。
