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 in vivo than in conventional in vitro 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 in vivo behavior of degradable materials, where the newly discovered information can guide the engineering of the next generation of imaging and therapeutic agents.

中文翻译：

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光学透明组织中的脂质体成像。

三维（3D）光学显微镜可用于了解和改善纳米药物的输送。然而，不能执行这种方法来分析组织中的脂质体，因为使组织透明以进行成像的处理步骤通常会去除脂质。在这里，我们开发了一个称为REMNANT的标签，该标签可对生物组织中的有机材料进行3D成像。我们展示了此标签在完整组织中脂质体的3D映射中的实用性。我们还表明，该标签能够监控包裹的治疗剂的释放。我们发现脂质体在体内组织中释放的货物比常规体外试验快100倍以上。这使我们能够设计具有增强的杀伤肿瘤相关巨噬细胞能力的脂质体制剂。我们的发展为研究在完整的生物环境中施用的有机材料的化学性质和药效学提供了新的机会。这种方法可洞察可降解材料的体内行为，其中新发现的信息可指导下一代成像和治疗剂的工程设计。