A Dual pH-Responsive DOX-Encapsulated Liposome Combined with Glucose Administration Enhanced Therapeutic Efficacy of Chemotherapy for Cancer
Luoping Zhai,1 Chuangwei Luo,1 Hannan Gao,1 Shuaifan Du,1 Jiyun Shi,2 Fan Wang1– 3 1Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, People’s Republic of China; 2Key...
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Dove Medical Press
2021
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oai:doaj.org-article:108fe0bbad2646c7a483a4e78bc443e42021-12-02T15:00:14ZA Dual pH-Responsive DOX-Encapsulated Liposome Combined with Glucose Administration Enhanced Therapeutic Efficacy of Chemotherapy for Cancer1178-2013https://doaj.org/article/108fe0bbad2646c7a483a4e78bc443e42021-05-01T00:00:00Zhttps://www.dovepress.com/a-dual-ph-responsive-dox-encapsulated-liposome-combined-with-glucose-a-peer-reviewed-fulltext-article-IJNhttps://doaj.org/toc/1178-2013Luoping Zhai,1 Chuangwei Luo,1 Hannan Gao,1 Shuaifan Du,1 Jiyun Shi,2 Fan Wang1– 3 1Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, People’s Republic of China; 2Key Laboratory of Protein and Peptide Pharmaceuticals, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Academy of Sciences, Beijing, 100101, People’s Republic of China; 3Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, 510005, People’s Republic of ChinaCorrespondence: Fan WangMedical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, People’s Republic of ChinaEmail wangfan@bjmu.edu.cnJiyun ShiKey Laboratory of Protein and Peptide Pharmaceuticals, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Academy of Sciences, Beijing, 100101, People’s Republic of ChinaEmail shijiyun@ibp.ac.cnBackground: The acidic microenvironment of cancer can promote tumor metastasis and drug resistance. Acidic tumor microenvironment-targeted therapy is currently an important means for treating tumors, inhibiting metastasis, and overcoming drug resistance. In this study, a dual pH-responsive DOX-encapsulated liposome (DOPE-DVar7-lip@DOX) was designed and fabricated for targeting the acidic tumor microenvironment. On the one hand, the response of acid-sensitive peptide (DVar7) to the acidic tumor microenvironment increased the uptake of liposomes in tumors and prolonged the retention time; on the other hand, the response of acid-sensitive phospholipid (DOPE) to the acidic tumor microenvironment improved the controlled release of DOX in tumors.Methods: The acid-sensitive peptide DVar7 modified liposomes can be obtained by simple incubation of DSPE-DVar7 with DOX-loaded DOPE liposomes (DOPE-lip@DOX). The tumor targeting of the dual pH-responsive liposome was investigated in vitro and in vivo by near-infrared fluorescence imaging. The tumor therapeutic efficacy of DOPE-DVar7-lip@DOX was evaluated in breast cancer mouse model using the traditional liposome as a control. Moreover, we regulated the tumor microenvironment acidity by injecting glucose to further enhance the therapeutic efficacy of cancer.Results: DVar7 can allosterically insert into the tumor cell membrane in the acidic tumor microenvironment to enhance the tumor uptake of liposomes and prolong the retention time of liposomes in tumor. In addition, the therapeutic efficacy of pH-responsive liposomes can be further enhanced by glucose injection regulating the acidity of tumor microenvironment.Discussion: DVar7 modified acid-sensitive nanocarriers combined with acidity regulation have great potential to improve drug resistance in clinical practice, thus improving the response rate and therapeutic effect of chemotherapy.Keywords: dual pH-responsive, liposomes, DOX, tumor, pH (low) insertion peptideZhai LLuo CGao HDu SShi JWang FDove Medical Pressarticledual ph-responsiveliposomesdoxtumorph (low) insertion peptideMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 3185-3199 (2021) |
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dual ph-responsive liposomes dox tumor ph (low) insertion peptide Medicine (General) R5-920 |
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dual ph-responsive liposomes dox tumor ph (low) insertion peptide Medicine (General) R5-920 Zhai L Luo C Gao H Du S Shi J Wang F A Dual pH-Responsive DOX-Encapsulated Liposome Combined with Glucose Administration Enhanced Therapeutic Efficacy of Chemotherapy for Cancer |
| description |
Luoping Zhai,1 Chuangwei Luo,1 Hannan Gao,1 Shuaifan Du,1 Jiyun Shi,2 Fan Wang1– 3 1Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, People’s Republic of China; 2Key Laboratory of Protein and Peptide Pharmaceuticals, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Academy of Sciences, Beijing, 100101, People’s Republic of China; 3Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, 510005, People’s Republic of ChinaCorrespondence: Fan WangMedical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, People’s Republic of ChinaEmail wangfan@bjmu.edu.cnJiyun ShiKey Laboratory of Protein and Peptide Pharmaceuticals, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Academy of Sciences, Beijing, 100101, People’s Republic of ChinaEmail shijiyun@ibp.ac.cnBackground: The acidic microenvironment of cancer can promote tumor metastasis and drug resistance. Acidic tumor microenvironment-targeted therapy is currently an important means for treating tumors, inhibiting metastasis, and overcoming drug resistance. In this study, a dual pH-responsive DOX-encapsulated liposome (DOPE-DVar7-lip@DOX) was designed and fabricated for targeting the acidic tumor microenvironment. On the one hand, the response of acid-sensitive peptide (DVar7) to the acidic tumor microenvironment increased the uptake of liposomes in tumors and prolonged the retention time; on the other hand, the response of acid-sensitive phospholipid (DOPE) to the acidic tumor microenvironment improved the controlled release of DOX in tumors.Methods: The acid-sensitive peptide DVar7 modified liposomes can be obtained by simple incubation of DSPE-DVar7 with DOX-loaded DOPE liposomes (DOPE-lip@DOX). The tumor targeting of the dual pH-responsive liposome was investigated in vitro and in vivo by near-infrared fluorescence imaging. The tumor therapeutic efficacy of DOPE-DVar7-lip@DOX was evaluated in breast cancer mouse model using the traditional liposome as a control. Moreover, we regulated the tumor microenvironment acidity by injecting glucose to further enhance the therapeutic efficacy of cancer.Results: DVar7 can allosterically insert into the tumor cell membrane in the acidic tumor microenvironment to enhance the tumor uptake of liposomes and prolong the retention time of liposomes in tumor. In addition, the therapeutic efficacy of pH-responsive liposomes can be further enhanced by glucose injection regulating the acidity of tumor microenvironment.Discussion: DVar7 modified acid-sensitive nanocarriers combined with acidity regulation have great potential to improve drug resistance in clinical practice, thus improving the response rate and therapeutic effect of chemotherapy.Keywords: dual pH-responsive, liposomes, DOX, tumor, pH (low) insertion peptide |
| format |
article |
| author |
Zhai L Luo C Gao H Du S Shi J Wang F |
| author_facet |
Zhai L Luo C Gao H Du S Shi J Wang F |
| author_sort |
Zhai L |
| title |
A Dual pH-Responsive DOX-Encapsulated Liposome Combined with Glucose Administration Enhanced Therapeutic Efficacy of Chemotherapy for Cancer |
| title_short |
A Dual pH-Responsive DOX-Encapsulated Liposome Combined with Glucose Administration Enhanced Therapeutic Efficacy of Chemotherapy for Cancer |
| title_full |
A Dual pH-Responsive DOX-Encapsulated Liposome Combined with Glucose Administration Enhanced Therapeutic Efficacy of Chemotherapy for Cancer |
| title_fullStr |
A Dual pH-Responsive DOX-Encapsulated Liposome Combined with Glucose Administration Enhanced Therapeutic Efficacy of Chemotherapy for Cancer |
| title_full_unstemmed |
A Dual pH-Responsive DOX-Encapsulated Liposome Combined with Glucose Administration Enhanced Therapeutic Efficacy of Chemotherapy for Cancer |
| title_sort |
dual ph-responsive dox-encapsulated liposome combined with glucose administration enhanced therapeutic efficacy of chemotherapy for cancer |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/108fe0bbad2646c7a483a4e78bc443e4 |
| work_keys_str_mv |
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