A soluble pH-responsive host-guest-based nanosystem for homogeneous exosomes capture with high-efficiency
A soluble pH-responsive host-guest-based nanosystem for homogeneous exosomes capture with high-efficiency
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DOI：
10.1016/j.cclet.2023.108129
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发表时间：
2023-06-17
影响因子：
9.1
通讯作者：
Qiao，Xiaoqiang
中科院分区：
文献类型：
--
作者：
Wang，Haiyan;Liang，Peng;Qiao，Xiaoqiang
外泌体为液体活检提供了理想的生物标志物。然而，高效捕获外泌体已被证明是极具挑战性的。在这里，我们报告了一个可溶性的pH响应的主机-客体为基础的纳米系统（PH-HGN）的外泌体的生理pH值周围的均匀隔离。PH-HGN由两个特定的功能化模块。首先，pH响应模块，聚甲基丙烯酸二甲氨基乙酯，提供均匀的捕获环境和尖锐的pH触发的自组装分离在水溶液中，以提高捕获效率和减少非特异性吸附。第二，与外泌体特异性抗体连接的主-客体模块聚丙烯酰胺偶氮苯和β-环糊精可以充当"可切割的桥"，以通过β-环糊精和AAAB部分之间的主-客体相互作用特异性捕获并随后快速释放捕获的外泌体。pH-HGN对来自两种不同细胞系的外泌体提供了高捕获效率，其对于H1299和MCF-7细胞来源的外泌体分别为90.2% ± 0.28%和87.0% ± 4.6%。分离的exosomes纯度为（1.49 ± 0.71）× 1011particles/µ g，是金标准超离心法（UC）的4.1倍。pH-HGN外泌体具有较好的完整性和生物活性。所开发的pH-HGN进一步成功地应用于区分肺癌患者和健康人。这些发现表明，pH-HGN在外泌体研究和下游应用中是一种有前途的策略。
Exosomes offer ideal biomarkers for liquid biopsies. However, high-efficient capture of exosomes has been proven to be extreme challenging. Here, we report a soluble pH-responsive host-guest-based nanosystem (pH-HGN) for homogeneous isolation of exosomes around physiological pH. The pH-HGN consists of two specifically functionalized modules. First, a pH-responsive module, poly-dimethylaminoethyl methacrylate, provides homogeneous capture circumstances and sharp pH-triggered self-assembly separation in aqueous solution to improve capture efficiency and reduce nonspecific adsorption. Second, a host-guest module, poly-acrylamide azobenzene andβ-cyclodextrin linked with exosomes-specific antibody, could act as the "cleavable bridge" to specific capture and subsequent rapid release of captured exosomes through host-guest interaction betweenβ-cyclodextrin and AAAB moieties. The pH-HGN offered high capture efficiencies for exosomes from two different cell lines, which were 90.2% ± 0.28% and 87.0% ± 4.6% for H1299 and MCF-7 cell-derived exosomes, respectively. The purity of isolated exosomes was (1.49 ± 0.71) × 1011particles/µg, which was 4.1 times higher compared with the gold standard ultracentrifugation (UC) method. Furthermore, the isolated exosomesviathe pH-HGN can preserve well integrity and biological activity. The developed pH-HGN was further successfully applied to differentiate lung cancer patients from healthy persons. These findings indicated that pH-HGN is a promising strategy in exosomes-based research and downstream applications.