Yang Yu, Zhang Miaomiao, Hong Zhiqiang, Mu Huiwen, Liu Ningang, Zhou Guangming, Miao Liyan, Li Shihong
Department of Clinical Pharmacology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Suzhou Medical College of Soochow University, Suzhou 215123, China.
iScience. 2025 Aug 9;28(9):113336. doi: 10.1016/j.isci.2025.113336. eCollection 2025 Sep 19.
The pH-sensitive drug release is an appealing strategy to enhance the therapy efficacy of anti-tumor liposomal drugs. In this study, we constructed the pH-sensitive magnesium-doxorubicin (Mg-DOX) liposomes by remote-loading of DOX into MgAc gradient liposomes. The prepared 100 nm Mg-DOX liposomes (Mg-DOX-Lip100) and folate receptor targeting Mg-DOX liposomes (FA-Mg-DOX-Lip100) were stable at physiological pH condition but gradually released DOX at acidic media. The FA-Mg-DOX-Lip100 exhibited much higher uptake by tumor cells and cytotoxicity than the Mg-DOX-Lip100. The Mg-DOX liposomes also showed stability in circulation in mice and delayed the growth of orthotopic EO771 tumor in C57BL/6 mice similar to Doxil-like liposomes at DOX dose of 5 mg/kg body weight every 4 days for 4 times, without observable morphologic change of the dissected organs at experiment endpoints. Thus, the pH-sensitive Mg-DOX liposomes have been successfully constructed and approved to be a potential antitumor delivery system to treat acidic tumors.
pH 敏感型药物释放是一种提高抗肿瘤脂质体药物治疗效果的有吸引力的策略。在本研究中，我们通过将阿霉素远程负载到醋酸镁梯度脂质体中构建了 pH 敏感型镁-阿霉素（Mg-DOX）脂质体。制备的 100 nm Mg-DOX 脂质体（Mg-DOX-Lip100）和叶酸受体靶向的 Mg-DOX 脂质体（FA-Mg-DOX-Lip100）在生理 pH 条件下稳定，但在酸性介质中逐渐释放阿霉素。与 Mg-DOX-Lip100 相比，FA-Mg-DOX-Lip100 在肿瘤细胞中的摄取和细胞毒性要高得多。Mg-DOX 脂质体在小鼠体内循环时也表现出稳定性，并且在每 4 天以 5 mg/kg 体重的剂量给予阿霉素，共给药 4 次的情况下，与类似 Doxil 的脂质体相似，可延缓 C57BL/6 小鼠原位 EO771 肿瘤的生长，在实验终点时解剖的器官未观察到形态学变化。因此，pH 敏感型 Mg-DOX 脂质体已成功构建，并被证明是一种治疗酸性肿瘤的潜在抗肿瘤递送系统。
