源自红细胞膜的生物纳米载体囊泡的抗体装载
Antibody-loading of biological nanocarrier vesicles derived from red-blood-cell membranes
AI总结：
本研究证明可将抗体装载到人红细胞膜衍生的外泌体模拟纳米囊泡中，并以单囊泡荧光方法量化装载率，为低免疫原性抗体递送提供新途径。
摘要：
抗体是针对药理学靶点的具有突破性的强效治疗剂，但在穿越免疫系统和细胞膜方面面临障碍。为克服这些问题，人们已探索多种策略，包括通过脂质体或生物伪装纳米颗粒进行穿梭递送。在此，我们证明了将抗体装载到源自人红细胞膜的外泌体模拟纳米囊泡中的可行性。将山羊抗鸡抗体装载到红细胞膜衍生的纳米囊泡中，并对其装载率进行表征，同时与更小的dUTP货物进行比较。采用双色重合荧光猝发方法，在单囊泡水平上分析纳米载体的装载率，克服了其尺寸异质性，并在52 nm的峰值半径下实现38%–41%的最高抗体装载率。经外泌体旋转柱额外纯化后，估计平均装载率为14%，且每个囊泡中超过两个抗体，与装载dUTP的纳米囊泡的结果相当。这些结果表明，利用新型、生物相容且低免疫原性的纳米载体增强治疗性抗体的生物分布和细胞内可达性是一条有前景的途径，适合大规模药理学应用。
英文摘要：
Antibodies, disruptive potent therapeutic agents against pharmacological targets, face a barrier crossing immune-system and cellular-membranes. To overcome these, various strategies have been explored including shuttling via liposomes or bio-camouflaged nanoparticles. Here, we demonstrate the feasibility to load antibodies into exosome-mimetic nanovesicles derived from human red-blood-cell-membranes. The goat-anti-chicken antibodies are loaded into erythrocyte-membrane derived nanovesicles and their loading yields are characterized and compared with smaller dUTP-cargo. Applying dual-color coincident fluorescence burst methodology, the loading yield of nanocarriers is profiled at single-vesicle level overcoming their size-heterogeneity and achieving a maximum of 38-41% antibody-loading yield at peak radius of 52 nm. The average of 14 % yield and more than two antibodies per vesicle is estimated, comparable to those of dUTP-loaded nanovesicles after additional purification through exosome-spin-column. These results suggest a promising route for enhancing biodistribution and intracellular accessibility for therapeutic antibodies using novel, biocompatible, and low-immunogenicity nanocarriers, suitable for large-scale pharmacological applications.
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