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:	Sun Y, Zhao Y, Teng S, Hao F, Zhang H, Meng F, Zhao X, Zheng X, Bi Y, Yao Y, Lee RJ, Teng L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	folic acid human serum albumin nanoparticles cabazitaxel folic acid receptor Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/fbaa2d1297e041d6898693ec69c4216b
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spelling	oai:doaj.org-article:fbaa2d1297e041d6898693ec69c4216b2021-12-02T09:39:49ZFolic acid receptor-targeted human serum albumin nanoparticle formulation of cabazitaxel for tumor therapy1178-2013https://doaj.org/article/fbaa2d1297e041d6898693ec69c4216b2018-12-01T00:00:00Zhttps://www.dovepress.com/folic-acid-receptor-targeted-human-serum-albumin-nanoparticle-formulat-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yating 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 receptorSun YZhao YTeng SHao FZhang HMeng FZhao XZheng XBi YYao YLee RJTeng LDove Medical Pressarticlefolic acidhuman serum albuminnanoparticlescabazitaxelfolic acid receptorMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 135-148 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	folic acid human serum albumin nanoparticles cabazitaxel folic acid receptor Medicine (General) R5-920
spellingShingle	folic acid human serum albumin nanoparticles cabazitaxel folic acid receptor Medicine (General) R5-920 Sun Y Zhao Y Teng S Hao F Zhang H Meng F Zhao X Zheng X Bi Y Yao Y Lee RJ Teng L Folic acid receptor-targeted human serum albumin nanoparticle formulation of cabazitaxel for tumor therapy
description	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
format	article
author	Sun Y Zhao Y Teng S Hao F Zhang H Meng F Zhao X Zheng X Bi Y Yao Y Lee RJ Teng L
author_facet	Sun Y Zhao Y Teng S Hao F Zhang H Meng F Zhao X Zheng X Bi Y Yao Y Lee RJ Teng L
author_sort	Sun Y
title	Folic acid receptor-targeted human serum albumin nanoparticle formulation of cabazitaxel for tumor therapy
title_short	Folic acid receptor-targeted human serum albumin nanoparticle formulation of cabazitaxel for tumor therapy
title_full	Folic acid receptor-targeted human serum albumin nanoparticle formulation of cabazitaxel for tumor therapy
title_fullStr	Folic acid receptor-targeted human serum albumin nanoparticle formulation of cabazitaxel for tumor therapy
title_full_unstemmed	Folic acid receptor-targeted human serum albumin nanoparticle formulation of cabazitaxel for tumor therapy
title_sort	folic acid receptor-targeted human serum albumin nanoparticle formulation of cabazitaxel for tumor therapy
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/fbaa2d1297e041d6898693ec69c4216b
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Folic acid receptor-targeted human serum albumin nanoparticle formulation of cabazitaxel for tumor therapy

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