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壳聚糖包被的透明质酸-多西他赛共轭纳米颗粒在CD44(+)癌细胞中的制备及生物学评价

Fabrication and biological evaluation of chitosan coated hyaluronic acid-docetaxel conjugate nanoparticles in CD44(+) cancer cells.

作者信息

Shabani Ravari Nazanin, Goodarzi Navid, Alvandifar Farhad, Amini Mohsen, Souri Effat, Khoshayand Mohammad Reza, Hadavand Mirzaie Zahra, Atyabi Fatemeh, Dinarvand Rassoul

机构信息

Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran.

Nanomedicine and Biomaterial Lab, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Daru. 2016 Jul 29;24(1):21. doi: 10.1186/s40199-016-0160-y.

DOI:10.1186/s40199-016-0160-y
PMID:27473554
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4966701/
Abstract

BACKGROUND

Hyaluronic acid (HA) has been used for target-specific drug delivery because of strong affinity to CD44, a marker in which overexpressed in cancer cells and cancer stem cells. Conjugation of HA to the cytotoxic agents via active targeting can improve efficacy, biodistribution, and water solubility. To be able to benefit from passive targeting as well, a nanoparticulate system by counter ion using a polycation like chitosan may lead to a perfect delivery system.

METHODS

Water soluble Hyaluronic acid-Docetaxel (HA-DTX) conjugate was prepared and used to formulate chitosan-coated HA-DTX nanoparticles by polyelectrolyte complex (PEC) method and optimized using Box-Behnken design. Biological evaluation of nanoparticles was done in CD44+ cancer cells.

RESULTS AND DISCUSSION

Biological evaluation of optimized formula showed IC50 of nanoparticles for 4 T1 and MCF-7 cell lines were 45.34 μM and 354.25 μM against 233.8 μM and 625.9 μM for DTX, respectively with increased cellular uptake showed by inverted confocal microscope.

CONCLUSION

Chitosan-coated HA-DTX nanoparticles were more effective against CD44+ cells than free DTX. Chitosan coated hyaluronic acid-docetaxel conjugate nanoparticles fabricated and evaluated in CD44+ cancer cells.

摘要

背景

透明质酸（HA）因其对CD44具有强亲和力而被用于靶向药物递送，CD44是一种在癌细胞和癌症干细胞中过表达的标志物。通过主动靶向将HA与细胞毒性药物偶联可以提高疗效、改善生物分布并提高水溶性。为了也能受益于被动靶向，使用壳聚糖等聚阳离子通过反离子形成纳米颗粒系统可能会产生一个完美的递送系统。

方法

制备了水溶性透明质酸-多西他赛（HA-DTX）偶联物，并通过聚电解质复合物（PEC）法用于制备壳聚糖包被的HA-DTX纳米颗粒，并使用Box-Behnken设计进行优化。在CD44+癌细胞中对纳米颗粒进行生物学评价。

结果与讨论

优化配方的生物学评价显示，纳米颗粒对4T1和MCF-7细胞系的IC50分别为45.34μM和354.25μM，而多西他赛分别为233.8μM和625.9μM，倒置共聚焦显微镜显示细胞摄取增加。

结论

壳聚糖包被的HA-DTX纳米颗粒对CD44+细胞比游离多西他赛更有效。制备了壳聚糖包被的透明质酸-多西他赛偶联纳米颗粒并在CD44+癌细胞中进行了评价。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cca6/4966701/445d17b6819a/40199_2016_160_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cca6/4966701/9c1d18b62af2/40199_2016_160_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cca6/4966701/3d29120bc683/40199_2016_160_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cca6/4966701/6a669382051c/40199_2016_160_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cca6/4966701/714f68367bda/40199_2016_160_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cca6/4966701/f88d69a5f8c5/40199_2016_160_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cca6/4966701/08702e28e671/40199_2016_160_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cca6/4966701/445d17b6819a/40199_2016_160_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cca6/4966701/9c1d18b62af2/40199_2016_160_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cca6/4966701/3d29120bc683/40199_2016_160_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cca6/4966701/6a669382051c/40199_2016_160_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cca6/4966701/714f68367bda/40199_2016_160_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cca6/4966701/f88d69a5f8c5/40199_2016_160_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cca6/4966701/08702e28e671/40199_2016_160_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cca6/4966701/445d17b6819a/40199_2016_160_Fig7_HTML.jpg

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