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

Abstract

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-DVar7lip@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.

Aptamer-Modified Erythrocyte Membrane-Coated pH-Sensitive Nanoparticles for c-Met-Targeted Therapy of Glioblastoma Multiforme

“…However, in the acid environment (e.g., pH 5.0), amphipathic PLGA-COO-could be reprotonated, become lipophilic, and destabilize NP-DOX. Thus NP-DOX could dissemble to rapidly release DOX under pH 5.0 and demonstrate a pH-sensitive behavior, which is favorable for tumor chemotherapy [37].…”

pH-Responsive Nanocarriers in Cancer Therapy

“…Many studies have focused on developing pH-sensitive liposomes for cancer therapy; for instance, Zhai et al [ 72 ] synthesized pH-responsive DOX-liposomes using the acid-sensitive peptide DVar7 (DOPE-DVar7-lip@DOX). The anti-cancer activity of DOPE-DVar7-lip@DOX was investigated in vitro and in vivo using flow cytometry and near-infrared (NIR) fluorescent imaging.…”

Updates on Responsive Drug Delivery Based on Liposome Vehicles for Cancer Treatment

“…Dual pH–pH responsive Dox-encapsulating liposomes containing responsive acid-sensitive peptide (DVar7) to acidic tumor microenvironments to increase the uptake and responsive acid-sensitive phospholipid (DOPE) for improved and controlled release of Dox in tumor cells was developed by Zhai et al The therapeutic efficacy of the formulations was found to be positively affected by glucose injection, regulating the acidity of the tumor microenvironment in the breast cancer mouse model [ 220 ].…”