A soluble pH-responsive host-guest-based nanosystem for homogeneous exosomes capture with high-efficiency |
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| Institution: | 1. College of Pharmaceutical Sciences, Key Laboratory of Public Health Safety of Hebei Province, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis, Ministry of Education, Hebei University, Baoding 071002, China;2. College of Basic Medical Science, Key Laboratory for Proteomics of Liaoning Province, Dalian Medical University, Dalian 116044, China;1. School of Chemistry, Xi''an Key Laboratory of Sustainable Energy Material Chemistry, Xi''an Jiao Tong University, Xi''an 710049, China;2. Instrumental Analysis Center, Xi''an Jiao Tong University, Xi''an 710049, China;3. School of Physics, Xi''an Jiao Tong University, Xi''an 710049, China;1. Key Laboratory of Tropical Translational Medicine of Ministry of Education, NHC Key Laboratory of Control of Tropical Diseases, School of Tropical Medicine, Micronano Technology Research Institute, School of Basic Medicine and Life Sciences, Hainan Medical University, Haikou 571199, China;2. Beadstar Biotechnology Hainan Province Co., Ltd., Haikou 570110, China;3. State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China;4. Economical Forest Cultivation and Utilization of 2011 Collaborative Innovation Center in Hunan Province, Hunan Key Laboratory of Biomedical Nanomaterials and Devices, Hunan University of Technology, Zhuzhou 412007, China;1. Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, China;2. Shenzhen Innovation Center for Small Molecule Drug Discovery Co., Ltd., Shenzhen 518110, China;3. Chemical Biology Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, China;4. Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China;5. Beijing National Laboratory for Molecular Sciences, Beijing 100190, China;1. School of Resources Environment and Materials, Guangxi University, Nanning 530004, China;2. School of Electronics Engineering, Guangxi University of Science and Technology, Liuzhou 545006, China;3. State Key Laboratory of Featured Metal Materials and Life-cycle Safety for Composite Structures, Guangxi University, Nanning 530004, China;4. Guangxi Higher Education Key Laboratory of High Performance Structural Materials and Heat Treatment & Surface Processing, Guangxi University, Nanning 53004, China;5. South Manganese Group Limited, Nanning 530029, China |
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| Abstract: | 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 and β-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 between β-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) × 1011 particles/µg, which was 4.1 times higher compared with the gold standard ultracentrifugation (UC) method. Furthermore, the isolated exosomes via the 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. |
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