Department Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Department of Clinical and Toxicological Analyses, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Biomed Pharmacother. 2019 Oct;118:109323. doi: 10.1016/j.biopha.2019.109323. Epub 2019 Aug 7.
Long circulating pH-sensitive liposomes have been shown to effectively deliver doxorubicin (DOX) to tumors and reduce its toxic effects. Folic acid receptors are upregulated in a wide variety of solid, epithelial tumors, including breast cancer. In order to improve liposomal endocytosis and antitumor activity, folic acid has been added to nanoparticles surfaces to exploit overexpression of folate receptors in tumor cells. The purpose of this study was to evaluate the antitumor activity in vitro and in vivo of long circulating pH-sensitive folate-coated DOX-loaded liposomes (SpHL-DOX-Fol) in a 4T1 breast cancer model system in vitro and in vivo. Biodistribution studies were performed and in vivo electrocardiographic parameters were evaluated. A higher tumor uptake for radiolabeled SpHL-Fol (Tc-SpHL-Fol) 4 h after intravenous administration was observed in comparision with non-folate-coated liposomes (Tc-SpHL). Antitumor activity showed that SpHL-DOX-Fol treatment led to a 68% growth arrest and drastically reduce pulmonary metastasis foci. Additionally, eletrocardiographic parameters analysis revealed no dispersion in the QT and QTc interval was observed in liposomal treated mice. In summary, this novel multifunctional nanoplatform deomonstrated higher tumor uptake and antitumor activity. SpHL-DOX-Fol represents a drug delivery platform to improve DOX tumor delivery and reduce dose-limiting toxicity.
长循环 pH 敏感脂质体已被证明能有效地将阿霉素（DOX）递送到肿瘤部位，并降低其毒性作用。叶酸受体在多种实体、上皮肿瘤中上调，包括乳腺癌。为了提高脂质体的内吞作用和抗肿瘤活性，已将叶酸添加到纳米颗粒表面，以利用肿瘤细胞中叶酸受体的过度表达。本研究的目的是在 4T1 乳腺癌模型系统中评估长循环 pH 敏感叶酸包覆 DOX 载药脂质体（SpHL-DOX-Fol）的体外和体内抗肿瘤活性。进行了生物分布研究，并评估了体内心电图参数。与非叶酸包覆脂质体（Tc-SpHL）相比，静脉注射后 4 小时，放射性标记的 SpHL-Fol（Tc-SpHL-Fol）在肿瘤中的摄取更高。抗肿瘤活性表明，SpHL-DOX-Fol 治疗导致 68%的肿瘤生长停滞，并大大减少肺转移灶。此外，心电图参数分析显示，脂质体处理的小鼠的 QT 和 QTc 间期没有离散。总之，这种新型多功能纳米平台显示出更高的肿瘤摄取和抗肿瘤活性。SpHL-DOX-Fol 代表了一种药物递送平台，可改善 DOX 肿瘤递送并降低剂量限制毒性。
