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使用基于纳米颗粒的多西环素递送系统增强宫颈癌的靶向治疗。

Enhanced targeted treatment of cervical cancer using nanoparticle-based doxycycline delivery system.

作者信息

Anjum Sadia, Akhtar Ayesha, Aldaqal Saleh M, Abduh Maisa S, Ahmad Hammad, Mustafa Riaz, Naseer Faiza, Sadia Maryam, Ahmad Tahir

机构信息

Department of Biology, University of Hail, Hail, Saudi Arabia.

Industrial Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan.

出版信息

Sci Rep. 2025 Jan 17;15(1):2318. doi: 10.1038/s41598-024-84203-8.

DOI:10.1038/s41598-024-84203-8
PMID:39824865
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11742058/
Abstract

This study investigates a nanoparticle-based doxycycline (DOX) delivery system targeting cervical cancer cells via the CD44 receptor. Molecular docking revealed a strong binding affinity between hyaluronic acid (HA) and CD44 (binding energy: -7.2 kJ/mol). Characterization of the HA-Chitosan nanoparticles showed a particle size of 284.6 nm, a zeta potential of 16.9 mV, and a polydispersity index of 0.314, with SEM confirming smooth surface morphology. The encapsulation efficiency of DOX-loaded nanoparticles was 89.32%, exhibiting a sustained release profile, with 67.45% released over 72 h in acidic conditions (pH 5.5). Cytotoxicity assays demonstrated a significant reduction in HeLa cell viability to 22% at 72 h, compared to 67% in normal HEK cells. Stability tests confirmed the maintenance of nanoparticle integrity and a consistent drug release profile over three months. Cell migration was reduced by 45%, and RT-PCR analysis revealed a 53% downregulation of TNF-α expression, suggesting effective targeting of inflammatory pathways. These results underscore the potential of HA-Chitosan-based DOX nanoparticles in improving cervical cancer treatment through enhanced targeted delivery and inhibition of tumor-promoting mechanisms.

摘要

本研究调查了一种基于纳米颗粒的多西环素(DOX)递送系统,该系统通过CD44受体靶向宫颈癌细胞。分子对接显示透明质酸(HA)与CD44之间具有很强的结合亲和力(结合能:-7.2 kJ/mol)。HA-壳聚糖纳米颗粒的表征显示粒径为284.6 nm,zeta电位为16.9 mV,多分散指数为0.314,扫描电子显微镜(SEM)证实表面形态光滑。载DOX纳米颗粒的包封率为89.32%,呈现出缓释特性,在酸性条件(pH 5.5)下72小时内释放67.45%。细胞毒性试验表明,与正常HEK细胞中的67%相比,HeLa细胞活力在72小时时显著降低至22%。稳定性测试证实纳米颗粒完整性在三个月内得以维持,药物释放曲线一致。细胞迁移减少了45%,逆转录-聚合酶链反应(RT-PCR)分析显示肿瘤坏死因子-α(TNF-α)表达下调53%,表明对炎症途径有有效靶向作用。这些结果强调了基于HA-壳聚糖的DOX纳米颗粒在通过增强靶向递送和抑制肿瘤促进机制改善宫颈癌治疗方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/11742058/05af650bf5d2/41598_2024_84203_Fig12_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/11742058/88f6939161cc/41598_2024_84203_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/11742058/05af650bf5d2/41598_2024_84203_Fig12_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/11742058/8105848ee5c1/41598_2024_84203_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/11742058/ca6c7d2168a9/41598_2024_84203_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/11742058/82c58c265ea7/41598_2024_84203_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/11742058/33b7f19af504/41598_2024_84203_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/11742058/d1bf9941eb90/41598_2024_84203_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/11742058/8102f6a1a967/41598_2024_84203_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/11742058/08e87dffc5bf/41598_2024_84203_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/11742058/bff549feb5c7/41598_2024_84203_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/11742058/72d823bd9c42/41598_2024_84203_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/11742058/2d6e288e5a8b/41598_2024_84203_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/11742058/88f6939161cc/41598_2024_84203_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49aa/11742058/05af650bf5d2/41598_2024_84203_Fig12_HTML.jpg

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