A Dual pH-Responsive DOX-Encapsulated Liposome Combined with Glucose Administration Enhanced Therapeutic Efficacy of Chemotherapy for Cancer

被引:31
作者
Zhai, Luoping [1 ,2 ]
Luo, Chuangwei [1 ,2 ]
Gao, Hannan [1 ,2 ]
Du, Shuaifan [1 ,2 ]
Shi, Jiyun [3 ]
Wang, Fan [1 ,2 ,3 ,4 ]
机构
[1] Peking Univ, Med Isotopes Res Ctr, Hlth Sci Ctr, Sch Basic Med Sci, Beijing 100191, Peoples R China
[2] Peking Univ, Sch Basic Med Sci, Hlth Sci Ctr, Dept Radiat Med, Beijing 100191, Peoples R China
[3] Acad Sci, CAS Ctr Excellence Biomacromol, Inst Biophys, Key Lab Prot & Peptide Pharmaceut, Beijing 100101, Peoples R China
[4] Guangzhou Regenerat Med & Hlth Guangdong Lab, Bioland Lab, Guangzhou 510005, Peoples R China
来源
INTERNATIONAL JOURNAL OF NANOMEDICINE | 2021年 / 16卷
基金
中国国家自然科学基金;
关键词
dual pH-responsive; liposomes; DOX; tumor; pH (low) insertion peptide; SENSITIVE LIPOSOMES; IN-VIVO; MAGNETIC-RESONANCE; WEAK ACID; DOXORUBICIN; DELIVERY; RESISTANCE; TUMORS; MICROENVIRONMENT; NANOPARTICLES;
D O I
10.2147/IJN.S303874
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
Background: 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.
引用
收藏
页码:3185 / 3199
页数:15
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