Institute of Biomaterials and Biomedical Engineering , University of Toronto , 164 College Street , Toronto , Ontario M5S 3G9 , Canada.
Department of Chemistry , University of Toronto , 80 St. George Street , Toronto , Ontario M5S 3H6 , Canada.
Nano Lett. 2020 Feb 12;20(2):1362-1369. doi: 10.1021/acs.nanolett.9b04853. Epub 2020 Jan 22.
Three-dimensional (3D) optical microscopy can be used to understand and improve the delivery of nanomedicine. However, this approach cannot be performed for analyzing liposomes in tissues because the processing step to make tissues transparent for imaging typically removes the lipids. Here, we developed a tag, termed REMNANT, that enables 3D imaging of organic materials in biological tissues. We demonstrated the utility of this tag for the 3D mapping of liposomes in intact tissues. We also showed that the tag is able to monitor the release of entrapped therapeutic agents. We found that liposomes release their cargo >100-fold faster in tissues than in conventional assays. This allowed us to design a liposomal formulation with enhanced ability to kill tumor associated macrophages. Our development opens up new opportunities for studying the chemical properties and pharmacodynamics of administered organic materials in an intact biological environment. This approach provides insight into the behavior of degradable materials, where the newly discovered information can guide the engineering of the next generation of imaging and therapeutic agents.
三维（3D）光学显微镜可用于了解和改善纳米医学的传递。然而，由于使组织透明以进行成像的处理步骤通常会除去脂质，因此无法使用这种方法来分析组织中的脂质体。在这里，我们开发了一种称为 REMNANT 的标记物，该标记物可实现生物组织中有机材料的 3D 成像。我们证明了该标记物在完整组织中对脂质体进行 3D 映射的实用性。我们还表明，该标记物能够监测被包裹的治疗剂的释放。我们发现，脂质体在组织中的释放速度比传统测定方法快 100 多倍。这使我们能够设计出一种具有增强杀死肿瘤相关巨噬细胞能力的脂质体配方。我们的发展为在完整的生物环境中研究给药有机材料的化学性质和药效动力学开辟了新的机会。这种方法使我们能够深入了解可降解材料的行为，新发现的信息可以指导下一代成像和治疗剂的工程设计。
