Al-Based Metal–Organic Nanoslice-Coupled Phospholipid Layer Enables Highly Enriched Biological External Vesicles

Systematic analysis of the information content of biological external vesicles (BEVs) is essential for understanding the complex relationships between metabolic processes and cells at a systemic level. Although considerable efforts have been made to enrich BEVs, their comprehensive analysis in a way that maintains and stabilizes information maintenance at high doses remains a challenge. To address this issue, we developed a metal–organic nanoslice-coupled exocytosis phospholipid layer method that utilized subtle interactions between the metal–organic nanoslice and the phospholipid molecular layer of the membrane to achieve the convenient and efficient enrichment of BEVs. The method bypassed the conventional ultracentrifugation and size exclusion separation and helped to highly preserve the internal information on BEVs. By integrating and analyzing the enriched BEVs for elements such as membrane proteins and endotoxins, the simplicity and robustness of the metal–organic nanoslice-coupled vesicle surface phospholipid layer technology were verified, which provided a reliable platform for studying the cellular events associated with outer vesicles and expanded the biological applications of the metal–organic nanoslice.