School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Int J Pharm. 2019 Oct 5;569:118595. doi: 10.1016/j.ijpharm.2019.118595. Epub 2019 Aug 5.
Breast cancer remains a major threat to women's health, and the incidence of breast cancer continues to increase each year. Paclitaxel (PTX) is commonly used to treat breast cancer, but shows limited solubility and is associated with major side effects, limiting its clinical applications. Photodynamic therapy (PDT) is a promising treatment for breast cancer but is limited by the poor solubility of photosensitizers and difficulties in targeting and enriching the tumor tissue with photosensitizers. Here, we prepared a new nanocarrier system using nanostructured lipid carriers (PTX@FA-NLC-PEG-Ce6) harboring PTX, chlorin e6 (Ce6), and folic acid-targeted head to overcome the limitations of PTX and Ce6 in hydrophobicity and increase the target efficiency of chemotherapy drugs and photosensitizers at the tumor. The results showed that the drug-loading system met the requirements for intravenous injection, had tumor targeting ability, and could be easily taken up by MDA-MB-231 cells. Moreover, Ce6 could be dissociated from the surface of the drug-loading system and evenly distributed in cells after a period of time when the nanostructured lipid carriers had entered lysosomes through endocytosis. Additionally, reactive oxygen species were then produced to induce PDT at a specific wavelength of illumination. In vitro pharmacodynamic experiments showed that combined PDT and chemotherapy had synergistic effects (combination index: 0.647). Furthermore, pharmacodynamic experiments in nude mice showed that the drug-loading system had ideal antitumor effects without obvious side effects. Thus, PTX@FA-NLC-PEG-Ce6 may have applications as a promising drug-loading system for PDT combined with chemotherapy in patients with breast cancer.
乳腺癌仍然是女性健康的主要威胁，乳腺癌的发病率每年持续增加。紫杉醇（PTX）常用于治疗乳腺癌，但溶解度有限，且存在严重的副作用，限制了其临床应用。光动力疗法（PDT）是一种有前途的乳腺癌治疗方法，但受到光敏剂溶解度低以及难以将光敏剂靶向和富集到肿瘤组织中的限制。在这里，我们制备了一种新型纳米载体系统，使用载有紫杉醇（PTX）、氯乙啶（Ce6）和叶酸靶向头的纳米结构化脂质载体（PTX@FA-NLC-PEG-Ce6），以克服 PTX 和 Ce6 的疏水性限制，并提高化疗药物和光敏剂在肿瘤部位的靶向效率。结果表明，载药系统符合静脉注射要求，具有肿瘤靶向能力，并且可以很容易地被 MDA-MB-231 细胞摄取。此外，Ce6 可以在一段时间后从载药系统的表面解离，并在纳米结构化脂质载体通过内吞作用进入溶酶体后均匀分布在细胞中。此外，还会产生活性氧物质，在特定的光照波长下诱导 PDT。体外药效学实验表明，联合 PDT 和化疗具有协同作用（组合指数：0.647）。此外，裸鼠药效学实验表明，载药系统具有理想的抗肿瘤作用，没有明显的副作用。因此，PTX@FA-NLC-PEG-Ce6 可能作为一种有前途的载药系统，用于联合化疗的 PDT 在乳腺癌患者中的应用。
