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透明质酸包覆壳聚糖纳米粒作为他莫昔芬的靶向载体对 MCF7 及 TMX 耐药 MCF7 细胞的作用

Hyaluronic acid-coated chitosan nanoparticles as targeted-carrier of tamoxifen against MCF7 and TMX-resistant MCF7 cells.

机构信息

Department of Chemistry, Shahrood Branch, Islamic Azad University, Shahrood, Iran.

Department of Biochemistry, Shahrood Branch, Islamic Azad University, Shahrood, Iran.

出版信息

J Mater Sci Mater Med. 2022 Feb 14;33(2):24. doi: 10.1007/s10856-022-06647-6.

DOI:10.1007/s10856-022-06647-6
PMID:35157166
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8843906/
Abstract

Tamoxifen (TMX) is used to treat hormone-receptor-positive breast cancers at early stages. This research aimed to assess the potential of NPs in targeted delivery of TMX against MCF7 and TMX-resistant MCF7 breast cancer cell lines. For this purpose, a targeted delivery system including chitosan NPs coated with hyaluronic acid (HA-CS NPs) was created and examined in vitro. Chitosan NPs were first fabricated and loaded with TMX using the ionic-gelation method to prepare a drug-delivery system. Then, TMX-loaded CS NPs were coated by crosslinking the amino groups of chitosan to the carboxylic group of hyaluronic acid. The developed TMX delivery system was then optimized and characterized for particle fabrication, drug release, and targeting against cancer cells. The HA-CS particle size was 210 nm and its zeta potential was +25 mv. The encapsulation efficiency of TMX in NPs was 55%. TMX released from the NPs in acidic pH (5-6) was higher than the physiological pH (7.4). The cytotoxic effect of TMX-loaded HA-CS NPs on MCF7 and TMX-resistant MCF7 cells was significantly higher than TMX-loaded CS NPs and free drug. The findings confirmed the significant suppressive impact of TMX-loaded HA-CS NPs on MCF7 and TMX-resistant MCF7 cancer cells compared to the TMX-loaded CS NPs and free TMX. Graphical abstract.

摘要

他莫昔芬（TMX）用于治疗早期激素受体阳性乳腺癌。本研究旨在评估 NP 对 MCF7 和 TMX 耐药 MCF7 乳腺癌细胞系靶向递送 TMX 的潜力。为此，创建并体外研究了包括壳聚糖 NPs 与透明质酸（HA-CS NPs）涂层的靶向递送系统。首先通过离子凝胶法制备壳聚糖 NPs 并负载 TMX，以制备药物递送系统。然后，通过壳聚糖的氨基与透明质酸的羧基交联将载有 TMX 的 CS NPs 进行涂层。然后优化并表征了开发的 TMX 递送系统的颗粒制备、药物释放和对癌细胞的靶向作用。HA-CS 颗粒大小为 210nm，其 ζ 电位为+25mv。TMX 在 NPs 中的包封效率为 55%。NP 中在酸性 pH（5-6）释放的 TMX 高于生理 pH（7.4）。载有 TMX 的 HA-CS NPs 对 MCF7 和 TMX 耐药 MCF7 细胞的细胞毒性作用明显高于载有 TMX 的 CS NPs 和游离药物。结果证实，与载有 TMX 的 CS NPs 和游离 TMX 相比，载有 TMX 的 HA-CS NPs 对 MCF7 和 TMX 耐药 MCF7 癌细胞具有显著的抑制作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6de5/8843906/83f418d73807/10856_2022_6647_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6de5/8843906/b6d8eef3d418/10856_2022_6647_Figa_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6de5/8843906/58409fafaa68/10856_2022_6647_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6de5/8843906/4426ce2a157a/10856_2022_6647_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6de5/8843906/31d37ef89c5e/10856_2022_6647_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6de5/8843906/e13b277dfa6b/10856_2022_6647_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6de5/8843906/83f418d73807/10856_2022_6647_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6de5/8843906/b6d8eef3d418/10856_2022_6647_Figa_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6de5/8843906/58409fafaa68/10856_2022_6647_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6de5/8843906/4426ce2a157a/10856_2022_6647_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6de5/8843906/31d37ef89c5e/10856_2022_6647_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6de5/8843906/e13b277dfa6b/10856_2022_6647_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6de5/8843906/83f418d73807/10856_2022_6647_Fig5_HTML.jpg

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