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用于多西他赛在转移性肺癌中进行位点特异性递送的丝蛋白盘状微粒

Silk protein discoidal microparticles for site-specific delivery of docetaxel in metastatic lung cancer.

作者信息

Cho Hyeyoun, Park Sanghyo, Park Jun Young, Hwang Yoonho, Kang Won Jun, Key Jaehong

机构信息

Department of Biomedical Engineering, Yonsei University, Wonju, 26493, Republic of Korea.

Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

出版信息

Mater Today Bio. 2025 Aug 9;34:102189. doi: 10.1016/j.mtbio.2025.102189. eCollection 2025 Oct.

DOI:10.1016/j.mtbio.2025.102189
PMID:40831990
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12359243/
Abstract

Silk proteins, such as silk sericin (SS) and silk fibroin (SF), have been shown to exhibit excellent biocompatibility, biodegradability, and low immunogenicity as drug delivery carriers. SS possesses antioxidant and anticancer adjuvant properties, whereas SF provides mechanical strength and structural stability, marking them as optimal materials for drug delivery systems. In this study, 3 μm discoidal silk protein particles (DSPs) based on silk sericin/silk fibroin (SS/SF) composites were developed for the loading of docetaxel (DTX). A comprehensive analysis was conducted to assess the morphological characteristics, particle size, zeta potential, drug loading content, and colloidal stability of the particles. studies utilizing human-derived non-small cell lung cancer (A549) and mouse-derived squamous cell carcinoma (SCC7) cell lines revealed that DTX-SS/SF-DSPs exhibited superior anticancer activity compared to both free DTX and DTX-SF-DSPs. biodistribution studies revealed that DTX-SS/SF-DSPs effectively accumulated in the lungs, with minimal accumulation in non-target organs, including the liver and kidneys. Anticancer efficacy evaluations showed a significant reduction in the number of tumor nodules and improvement in survival rates. Furthermore, histopathological analysis confirmed reduced inflammatory responses and the absence of major organ toxicity, demonstrating excellent biocompatibility. In conclusion, SS/SF-DSPs are a promising drug delivery system that can improve the therapeutic efficacy of anticancer drugs with minimal side effects, which can present a new paradigm in lung cancer treatment.

摘要

丝蛋白,如丝胶蛋白(SS)和丝素蛋白(SF),已被证明作为药物递送载体具有优异的生物相容性、生物降解性和低免疫原性。SS具有抗氧化和抗癌佐剂特性,而SF提供机械强度和结构稳定性,使其成为药物递送系统的理想材料。在本研究中,开发了基于丝胶蛋白/丝素蛋白(SS/SF)复合材料的3μm盘状丝蛋白颗粒(DSPs)用于多西他赛(DTX)的负载。对颗粒的形态特征、粒径、zeta电位、载药量和胶体稳定性进行了全面分析。利用人源非小细胞肺癌(A549)和小鼠源鳞状细胞癌(SCC7)细胞系的研究表明,与游离DTX和DTX-SF-DSPs相比,DTX-SS/SF-DSPs表现出优异的抗癌活性。生物分布研究表明,DTX-SS/SF-DSPs有效地在肺部积累,在包括肝脏和肾脏在内的非靶器官中积累最少。抗癌疗效评估显示肿瘤结节数量显著减少,生存率提高。此外,组织病理学分析证实炎症反应减轻且无主要器官毒性,表明具有优异的生物相容性。总之,SS/SF-DSPs是一种有前途的药物递送系统,可在最小副作用的情况下提高抗癌药物的治疗效果,这可为肺癌治疗提供一种新的范例。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55f5/12359243/76c60e802b8a/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55f5/12359243/75f62f22b0d3/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55f5/12359243/e156fd675236/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55f5/12359243/de18a3c85c57/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55f5/12359243/71ce6db1e7f8/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55f5/12359243/034878a0d5f5/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55f5/12359243/167db78d465b/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55f5/12359243/76c60e802b8a/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55f5/12359243/75f62f22b0d3/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55f5/12359243/e156fd675236/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55f5/12359243/de18a3c85c57/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55f5/12359243/71ce6db1e7f8/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55f5/12359243/034878a0d5f5/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55f5/12359243/167db78d465b/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55f5/12359243/76c60e802b8a/gr6.jpg

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本文引用的文献

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Biomimetic Silk Nanoparticle Manufacture: Calcium Ion-Mediated Assembly.仿生丝纳米颗粒的制备:钙离子介导的组装
ACS Biomater Sci Eng. 2025 Mar 10;11(3):1847-1856. doi: 10.1021/acsbiomaterials.4c02175. Epub 2025 Jan 30.
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Repurposing of sericin combined with dactolisib or vitamin D to combat non-small lung cancer cells through computational and biological investigations.通过计算和生物学研究,将丝胶与达妥昔单抗或维生素 D 联合再利用,以对抗非小细胞肺癌细胞。
Sci Rep. 2024 Nov 7;14(1):27034. doi: 10.1038/s41598-024-76947-0.
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Development of pH-responsive Eudragit S100-functionalized silk fibroin nanoparticles as a prospective drug delivery system.
pH 响应性 Eudragit S100 功能化丝素纳米粒的制备及其作为一种有前景的药物传递系统。
PLoS One. 2024 May 23;19(5):e0303177. doi: 10.1371/journal.pone.0303177. eCollection 2024.
4
Exploring the apoptotic effects of sericin on HCT116 cells through comprehensive nanostring transcriptomics and proteomics analysis.通过全面的纳米串转录组学和蛋白质组学分析探索丝胶对 HCT116 细胞的凋亡作用。
Sci Rep. 2024 Jan 29;14(1):2366. doi: 10.1038/s41598-024-52789-8.
5
In vitro and in vivo anti-colorectal cancer effect of the newly synthesized sericin/propolis/fluorouracil nanoplatform through modulation of PI3K/AKT/mTOR pathway.新合成的丝胶/蜂胶/氟尿嘧啶纳米平台通过调节 PI3K/AKT/mTOR 通路对结直肠癌细胞的体内外抗癌作用。
Sci Rep. 2024 Jan 29;14(1):2433. doi: 10.1038/s41598-024-52722-z.
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Cancer statistics, 2024.2024年癌症统计数据。
CA Cancer J Clin. 2024 Jan-Feb;74(1):12-49. doi: 10.3322/caac.21820. Epub 2024 Jan 17.
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Silk wastes and autoclaved degumming as an alternative for a sustainable silk process.丝废料和高压蒸煮脱胶作为可持续丝工艺的替代方法。
Sci Rep. 2023 Sep 15;13(1):15296. doi: 10.1038/s41598-023-41762-6.
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Pulling and analyzing silk fibers from aqueous solution using a robotic device.使用机器人设备从水溶液中提取和分析丝纤维。
Int J Biol Macromol. 2023 Oct 1;250:126161. doi: 10.1016/j.ijbiomac.2023.126161. Epub 2023 Aug 6.
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Microparticles of Sericin-Dextran Conjugate for Improving the Solubility of Antiviral Drug.用于提高抗病毒药物溶解度的丝胶蛋白-葡聚糖共轭物微粒
J Funct Biomater. 2023 May 24;14(6):292. doi: 10.3390/jfb14060292.
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Emerging frontiers in drug delivery with special focus on novel techniques for targeted therapies.新兴的药物输送前沿领域,特别关注靶向治疗的新技术。
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