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阿霉素和负载NFL-TBS.40-63肽的金纳米颗粒作为胶质母细胞瘤的多模态治疗方法。

Doxorubicin and NFL-TBS.40-63 peptide loaded gold nanoparticles as a multimodal therapy of glioblastoma.

作者信息

Moutaoukil Myriam El, Lolli Maria Grazia, D'Amone Stefania, Khan Memona, Grillo Roberta, Eyer Joel, Grieco Maddalena, Ursini Ornella, Spadavecchia Jolanda, Cortese Barbara

机构信息

CNRS, NBD-CSPBAT, Laboratory of Chemistry, Structures and Properties of Biomaterials and Therapeutic Agents University Paris13, Sorbonne Paris Nord, Bobigny, France.

National Research Council - Institute of Nanotechnology (CNR Nanotec), c/o Department of Physics "E. Fermi", University Sapienza, Pz.le Aldo Moro 5, 00185, Rome, Italy.

出版信息

Discov Nano. 2025 Apr 28;20(1):72. doi: 10.1186/s11671-025-04249-z.

DOI:10.1186/s11671-025-04249-z
PMID:40293574
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12037963/
Abstract

Conventional treatments for glioblastoma (GBM) are hindered by systemic toxicity, limited blood-brain barrier penetration, and therapeutic resistance. To address these challenges, we developed dual-functionalized gold nanoparticles (AuNPs) conjugated with a biotinylated NFL-TBS.40-63 peptide and the chemotherapeutic agent doxorubicin. This platform integrates targeted delivery and therapeutic action to enhance efficacy while minimising off-target effects. Our findings reveal superior cellular uptake, dose- and time-dependent cytotoxicity, and apoptosis induction in GBM cells compared to mono-functionalized counterparts. Furthermore, pH-sensitive drug release profiles underscore the system's potential to exploit the tumour microenvironment's acidic conditions for precise drug delivery. Comprehensive characterisation confirmed the stability, biocompatibility, and functional efficacy of the dual-functionalized AuNPs. This study highlights the promise of these nanoconjugates as a multimodal approach to GBM therapy, paving the way for further translational research in nanomedicine.

摘要

胶质母细胞瘤（GBM）的传统治疗方法受到全身毒性、血脑屏障穿透有限和治疗耐药性的阻碍。为应对这些挑战，我们开发了与生物素化的NFL-TBS.40-63肽和化疗药物阿霉素偶联的双功能化金纳米颗粒（AuNPs）。该平台整合了靶向递送和治疗作用，以提高疗效，同时将脱靶效应降至最低。我们的研究结果显示，与单功能化的对应物相比，GBM细胞对其细胞摄取更高、具有剂量和时间依赖性细胞毒性以及诱导细胞凋亡。此外，pH敏感的药物释放曲线突出了该系统利用肿瘤微环境酸性条件进行精确药物递送的潜力。全面表征证实了双功能化AuNPs的稳定性、生物相容性和功能功效。这项研究突出了这些纳米偶联物作为GBM治疗的多模态方法的前景，为纳米医学的进一步转化研究铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7414/12037963/e0f855f15521/11671_2025_4249_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7414/12037963/e5f184df9bb0/11671_2025_4249_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7414/12037963/37ab886db886/11671_2025_4249_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7414/12037963/db469642cdb3/11671_2025_4249_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7414/12037963/f96f96bd8b1b/11671_2025_4249_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7414/12037963/db784e3d9ae4/11671_2025_4249_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7414/12037963/e0f855f15521/11671_2025_4249_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7414/12037963/e5f184df9bb0/11671_2025_4249_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7414/12037963/37ab886db886/11671_2025_4249_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7414/12037963/db469642cdb3/11671_2025_4249_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7414/12037963/f96f96bd8b1b/11671_2025_4249_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7414/12037963/db784e3d9ae4/11671_2025_4249_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7414/12037963/e0f855f15521/11671_2025_4249_Fig6_HTML.jpg

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本文引用的文献

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Nanomaterials (Basel). 2025 Jan 17;15(2):133. doi: 10.3390/nano15020133.
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Biotin-functionalized nanoparticles: an overview of recent trends in cancer detection.生物素功能化纳米颗粒：癌症检测的最新趋势概述。
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A recent insight of applications of gold nanoparticles in glioblastoma multiforme therapy.金纳米粒子在多形性胶质母细胞瘤治疗中的应用的最新研究进展。
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Spectroscopic Assessment of Doxorubicin (DOX)-Gemcitabine (GEM) Gold Complex Nanovector as Diagnostic Tool of Galectin-1 Biomarker.多柔比星（DOX）-吉西他滨（GEM）金络合物纳米载体作为半乳糖凝集素-1生物标志物诊断工具的光谱评估
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The use of liposomes functionalized with the NFL-TBS.40-63 peptide as a targeting agent to cross the in vitro blood-brain barrier and target glioblastoma cells.使用用NFL-TBS.40-63肽功能化的脂质体作为靶向剂，以穿过体外血脑屏障并靶向胶质母细胞瘤细胞。
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Nanomedicine in cancer therapy.癌症治疗中的纳米医学。
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