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Blood TfR+ exosomes separated by a pH-responsive method deliver chemotherapeutics for tumor therapy
Blood transferrin receptor-positive (TfR+) exosomes are a kind of optimized drug delivery vector compared with other kinds of exosomes due to their easy access and high bio-safety. Their application facilitates the translation from bench to bedside of exosome-based delivery vehicles. Methods: In thi...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831460/ https://www.ncbi.nlm.nih.gov/pubmed/31695794 http://dx.doi.org/10.7150/thno.37220 |
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author | Yang, Lijun Han, Donglin Zhan, Qi Li, Xueping Shan, Peipei Hu, Yunjie Ding, Han Wang, Yu Zhang, Lei Zhang, Yuan Xue, Sheng Zhao, Jin Hou, Xin Wang, Yin Li, Peifeng Yuan, Xubo Qi, Hongzhao |
author_facet | Yang, Lijun Han, Donglin Zhan, Qi Li, Xueping Shan, Peipei Hu, Yunjie Ding, Han Wang, Yu Zhang, Lei Zhang, Yuan Xue, Sheng Zhao, Jin Hou, Xin Wang, Yin Li, Peifeng Yuan, Xubo Qi, Hongzhao |
author_sort | Yang, Lijun |
collection | PubMed |
description | Blood transferrin receptor-positive (TfR+) exosomes are a kind of optimized drug delivery vector compared with other kinds of exosomes due to their easy access and high bio-safety. Their application facilitates the translation from bench to bedside of exosome-based delivery vehicles. Methods: In this study, a pH-responsive superparamagnetic nanoparticles cluster (denoted as SMNC)-based method was developed for the precise and mild separation of blood TfR+ exosomes. Briefly, multiple superparamagnetic nanoparticles (SPMNs) labeled with transferrins (Tfs) could precisely bind to blood TfR+ exosomes to form an exosome-based cluster due to the specific recognition of TfR by Tf. They could realize the precise magnetic separation of blood TfR+ exosomes. More importantly, the pH-responsive dissociation characteristic of Tf and TfR led to the mild collapse of clusters to obtain pure blood TfR+ exosomes. Results: Blood TfR+ exosomes with high purity and in their original state were successfully obtained through the pH-responsive SMNC-based method. These can load Doxorubicin (DOX) with a loading capacity of ~10% and dramatically increase the tumor accumulation of DOX in tumor-bearing mice because of their innate passive-targeting ability. In addition, blood TfR+ exosomes changed the biodistribution of DOX leading to the reduction of side effects. Compared with free DOX, DOX-loaded blood TfR+ exosomes showed much better tumor inhibition effects on tumor-bearing mice. Conclusion: Taking advantage of the pH-responsive binding and disaggregation characteristics of Tf and TfR, the SMNC-based method can precisely separate blood TfR+ exosomes with high purity and in their original state. The resulting blood TfR+ exosomes showed excellent bio-safety and enable the efficient delivery of chemotherapeutics to tumors, facilitating the clinical translation of exosome-based drug delivery systems. |
format | Online Article Text |
id | pubmed-6831460 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-68314602019-11-06 Blood TfR+ exosomes separated by a pH-responsive method deliver chemotherapeutics for tumor therapy Yang, Lijun Han, Donglin Zhan, Qi Li, Xueping Shan, Peipei Hu, Yunjie Ding, Han Wang, Yu Zhang, Lei Zhang, Yuan Xue, Sheng Zhao, Jin Hou, Xin Wang, Yin Li, Peifeng Yuan, Xubo Qi, Hongzhao Theranostics Research Paper Blood transferrin receptor-positive (TfR+) exosomes are a kind of optimized drug delivery vector compared with other kinds of exosomes due to their easy access and high bio-safety. Their application facilitates the translation from bench to bedside of exosome-based delivery vehicles. Methods: In this study, a pH-responsive superparamagnetic nanoparticles cluster (denoted as SMNC)-based method was developed for the precise and mild separation of blood TfR+ exosomes. Briefly, multiple superparamagnetic nanoparticles (SPMNs) labeled with transferrins (Tfs) could precisely bind to blood TfR+ exosomes to form an exosome-based cluster due to the specific recognition of TfR by Tf. They could realize the precise magnetic separation of blood TfR+ exosomes. More importantly, the pH-responsive dissociation characteristic of Tf and TfR led to the mild collapse of clusters to obtain pure blood TfR+ exosomes. Results: Blood TfR+ exosomes with high purity and in their original state were successfully obtained through the pH-responsive SMNC-based method. These can load Doxorubicin (DOX) with a loading capacity of ~10% and dramatically increase the tumor accumulation of DOX in tumor-bearing mice because of their innate passive-targeting ability. In addition, blood TfR+ exosomes changed the biodistribution of DOX leading to the reduction of side effects. Compared with free DOX, DOX-loaded blood TfR+ exosomes showed much better tumor inhibition effects on tumor-bearing mice. Conclusion: Taking advantage of the pH-responsive binding and disaggregation characteristics of Tf and TfR, the SMNC-based method can precisely separate blood TfR+ exosomes with high purity and in their original state. The resulting blood TfR+ exosomes showed excellent bio-safety and enable the efficient delivery of chemotherapeutics to tumors, facilitating the clinical translation of exosome-based drug delivery systems. Ivyspring International Publisher 2019-10-14 /pmc/articles/PMC6831460/ /pubmed/31695794 http://dx.doi.org/10.7150/thno.37220 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Yang, Lijun Han, Donglin Zhan, Qi Li, Xueping Shan, Peipei Hu, Yunjie Ding, Han Wang, Yu Zhang, Lei Zhang, Yuan Xue, Sheng Zhao, Jin Hou, Xin Wang, Yin Li, Peifeng Yuan, Xubo Qi, Hongzhao Blood TfR+ exosomes separated by a pH-responsive method deliver chemotherapeutics for tumor therapy |
title | Blood TfR+ exosomes separated by a pH-responsive method deliver chemotherapeutics for tumor therapy |
title_full | Blood TfR+ exosomes separated by a pH-responsive method deliver chemotherapeutics for tumor therapy |
title_fullStr | Blood TfR+ exosomes separated by a pH-responsive method deliver chemotherapeutics for tumor therapy |
title_full_unstemmed | Blood TfR+ exosomes separated by a pH-responsive method deliver chemotherapeutics for tumor therapy |
title_short | Blood TfR+ exosomes separated by a pH-responsive method deliver chemotherapeutics for tumor therapy |
title_sort | blood tfr+ exosomes separated by a ph-responsive method deliver chemotherapeutics for tumor therapy |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831460/ https://www.ncbi.nlm.nih.gov/pubmed/31695794 http://dx.doi.org/10.7150/thno.37220 |
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