Folic acid receptor-targeted human serum albumin nanoparticle formulation of cabazitaxel for tumor therapy
Yating Sun,1 Yarong Zhao,1 Shanshan Teng,1 Fei Hao,1 Huan Zhang,1 Fanchao Meng,1 Xiuting Zhao,1 Xiaolong Zheng,1 Ye Bi,1 Yicheng Yao,2 Robert J Lee,1,3 Lesheng Teng1 1School of Life Sciences, Jilin University, Changchun, Jilin, China; 2Acalanes High School, Lafayette, CA, USA; 3Division of Pharmace...
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| Autores principales: | , , , , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Dove Medical Press
2018
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/fbaa2d1297e041d6898693ec69c4216b |
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| Sumario: | Yating Sun,1 Yarong Zhao,1 Shanshan Teng,1 Fei Hao,1 Huan Zhang,1 Fanchao Meng,1 Xiuting Zhao,1 Xiaolong Zheng,1 Ye Bi,1 Yicheng Yao,2 Robert J Lee,1,3 Lesheng Teng1 1School of Life Sciences, Jilin University, Changchun, Jilin, China; 2Acalanes High School, Lafayette, CA, USA; 3Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA Background: We previously developed cabazitaxel (CTX)-loaded human serum albumin nanoparticles (NPs-CTX) via a self-assembly method, and these NPs showed efficacy in prostate cancer therapy. Many studies have shown that the levels of folic acid (FA) receptor on the surface of various tumor cells are high. Therefore, FA-modified NPs-CTX may have enhanced antitumor effects compared with unmodified NPs-CTX. Methods: NPs-CTX were first prepared via self-assembly, and FA was conjugated on the surface of NPs-CTX through the -NH2 groups of the NPs to produce FA-NPs-CTX. The FA-NPs-CTX were evaluated in tumor cells with high FA receptor (FR) expression in vitro and in vivo. Results: Both NPs-CTX and FA-NPs-CTX exhibited good stability and morphology. Drug release from the NPs was not affected by FA conjugation. Compared with CTX dissolved in a mixture of Tween 80 and 13% ethanol (w/w) at a ratio of 1:4 (v/v) (Tween-CTX), the two nanoformulations had lower lytic activity against normal red blood cells. However, FA-NPs-CTX showed greater inhibition of tumor cells with overexpressed FR, compared with NPs-CTX, in the cytotoxicity experiments. Moreover, the cellular uptake of FA-NPs-CTX was enhanced through FR-mediated endocytosis in HeLa cells in vitro and HeLa xenograft tumors in vivo. Although Tween-CTX exhibited tumor growth inhibition similar to FA-NPs-CTX in vivo, this inhibition also caused adverse side effects; the median lethal dose (LD50) of Tween-CTX to mice was 5.68 mg/kg, while FA-NPs-CTX-treated mice survived at doses exceeding 400 mg/kg. Conclusion: The results showed that FA-NPs-CTX caused inhibition of tumor growth in a manner similar to that of Tween-CTX; however, the safety and tolerability of CTX were greatly improved by FA conjugation compared with those of Tween-CTX. In summary, FA-NPs-CTX have great potential in CTX delivery, and this formulation is a promising candidate for the treatment of cancers with high FR levels. Keywords: folic acid, human serum albumin, nanoparticles, cabazitaxel, folic acid receptor |
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