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基于内体 pH 响应的 Fe 修饰透明质酸纳米粒用于阿霉素传递

Endosomal pH-Responsive Fe-Based Hyaluronate Nanoparticles for Doxorubicin Delivery.

机构信息

Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Bucheon-si 14662, Gyeonggi-do, Korea.

Department of Biomedical-Chemical Engineering, The Catholic University of Korea, 43 Jibong-ro, Bucheon-si 14662, Gyeonggi-do, Korea.

出版信息

Molecules. 2021 Jun 10;26(12):3547. doi: 10.3390/molecules26123547.

DOI:10.3390/molecules26123547
PMID:34200716
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8229704/
Abstract

In this study, we report pH-responsive metal-based biopolymer nanoparticles (NPs) for tumor-specific chemotherapy. Here, aminated hyaluronic acid (aHA) coupled with 2,3-dimethylmaleic anhydride (DMA, as a pH-responsive moiety) (aHA-DMA) was electrostatically complexed with ferrous chloride tetrahydrate (FeCl/4HO, as a chelating metal) and doxorubicin (DOX, as an antitumor drug model), producing DOX-loaded Fe-based hyaluronate nanoparticles (DOX@aHA-DMA/Fe NPs). Importantly, the DOX@aHA-DMA/Fe NPs improved tumor cellular uptake due to HA-mediated endocytosis for tumor cells overexpressing CD44 receptors. As a result, the average fluorescent DOX intensity observed in MDA-MB-231 cells (with CD44 receptors) was ~7.9 × 10 (DOX@HA/Fe NPs, without DMA), ~8.1 × 10 (DOX@aHA-DMA/Fe NPs), and ~9.3 × 10 (DOX@aHA-DMA/Fe NPs). Furthermore, the DOX@aHA-DMA/Fe NPs were destabilized due to ionic repulsion between Fe and DMA-detached aHA (i.e., positively charged free aHA) in the acidic environment of tumor cells. This event accelerated the release of DOX from the destabilized NPs. Our results suggest that these NPs can be promising tumor-targeting drug carriers responding to acidic endosomal pH.

摘要

在这项研究中，我们报告了 pH 响应型金属基生物聚合物纳米粒子（NPs）用于肿瘤特异性化疗。在这里，氨基化透明质酸（aHA）与 2,3-二甲基马来酸酐（DMA，作为 pH 响应部分）（aHA-DMA）通过静电相互作用与四水合氯化亚铁（FeCl/4HO，作为螯合金属）和阿霉素（DOX，作为抗肿瘤药物模型）复合，生成负载 DOX 的基于 Fe 的透明质酸盐纳米粒子（DOX@aHA-DMA/Fe NPs）。重要的是，由于 HA 介导的肿瘤细胞过表达 CD44 受体的内吞作用，DOX@aHA-DMA/Fe NPs 提高了肿瘤细胞摄取 DOX 的能力。结果，在 MDA-MB-231 细胞（具有 CD44 受体）中观察到的平均荧光 DOX 强度约为 7.9×10（DOX@HA/Fe NPs，无 DMA），约为 8.1×10（DOX@aHA-DMA/Fe NPs），和约为 9.3×10（DOX@aHA-DMA/Fe NPs）。此外，由于肿瘤细胞酸性环境中 Fe 和与 DMA 分离的 aHA（即带正电荷的游离 aHA）之间的离子排斥作用，DOX@aHA-DMA/Fe NPs 不稳定。该事件加速了不稳定 NPs 中 DOX 的释放。我们的研究结果表明，这些 NPs 可作为响应酸性内体 pH 的有前途的肿瘤靶向药物载体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26f0/8229704/809520696c87/molecules-26-03547-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26f0/8229704/b4c44b399478/molecules-26-03547-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26f0/8229704/31f091a91857/molecules-26-03547-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26f0/8229704/be19b48cb9bd/molecules-26-03547-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26f0/8229704/d2fe5e7f6f2c/molecules-26-03547-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26f0/8229704/53c7f23b61ab/molecules-26-03547-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26f0/8229704/809520696c87/molecules-26-03547-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26f0/8229704/b4c44b399478/molecules-26-03547-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26f0/8229704/31f091a91857/molecules-26-03547-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26f0/8229704/be19b48cb9bd/molecules-26-03547-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26f0/8229704/d2fe5e7f6f2c/molecules-26-03547-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26f0/8229704/53c7f23b61ab/molecules-26-03547-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/26f0/8229704/809520696c87/molecules-26-03547-g006.jpg

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