期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 569, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2019.118595
关键词
Paclitaxel; Photodynamic therapy; Nanostructured lipid carriers; Intravenous injection; Breast cancer
资金
- National Natural Science Foundation of China [81573619]
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 ma the requirements for intravenous injection, had tumor targeting ability, and could be easily taken up by MDA-MB231 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.
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