A Dual pH-Responsive DOX-Encapsulated Liposome Combined with Glucose Administration Enhanced Therapeutic Efficacy of Chemotherapy for Cancer.
A Dual pH-Responsive DOX-Encapsulated Liposome Combined with Glucose Administration Enhanced Therapeutic Efficacy of Chemotherapy for Cancer.
复制标题
双重 pH 响应 DOX 封装的脂质体与葡萄糖给药相结合增强了癌症化疗的治疗效果。
DOI：
10.2147/ijn.s303874
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发表时间：
2021
影响因子：
8
通讯作者：
Wang F
中科院分区：
文献类型：
--
作者：
Zhai L;Luo C;Gao H;Du S;Shi J;Wang F
癌症的酸性微环境可以促进肿瘤转移和耐药。酸性肿瘤微环境靶向治疗是目前治疗肿瘤、抑制转移、克服耐药性的重要手段。在这项研究中，设计和制造了一种双 pH 响应 DOX 封装的脂质体 (DOPE-DVar7-lip@DOX)，用于靶向酸性肿瘤微环境。一方面，酸敏感肽（DVar7）对酸性肿瘤微环境的反应增加了肿瘤中脂质体的摄取并延长了保留时间；另一方面，酸敏感磷脂（DOPE）对酸性肿瘤微环境的反应改善了DOX在肿瘤中的控释。通过将 DSPE-DVar7 与负载 DOX 的 DOPE 脂质体 (DOPE-lip@DOX) 简单孵育即可获得酸敏感肽 DVar7 修饰的脂质体。通过近红外荧光成像在体外和体内研究双 pH 响应脂质体的肿瘤靶向性。使用传统脂质体作为对照，在乳腺癌小鼠模型中评估 DOPE-DVar7-lip@DOX 的肿瘤治疗效果。此外，我们通过注射葡萄糖来调节肿瘤微环境酸度，进一步增强癌症的治疗效果。 DVar7可以在酸性肿瘤微环境中变构插入肿瘤细胞膜，增强肿瘤对脂质体的摄取，延长脂质体在肿瘤中的保留时间。此外，通过葡萄糖注射调节肿瘤微环境的酸度可以进一步增强pH响应性脂质体的治疗效果。 DVar7修饰的酸敏感纳米载体结合酸度调节在临床上具有改善耐药性的巨大潜力，从而提高化疗的反应率和治疗效果。
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. 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. 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. 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.