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一种结合载秋水仙碱脂质纳米胶囊和BIOT-NFL肽以靶向胶质母细胞瘤的潜在纳米递送系统的开发。

Development of a potential nano-based delivery system combining Colchicine-loaded lipid nanocapsules and BIOT-NFL-peptide to target glioblastoma.

作者信息

Alnemeh-Al Ali H, Bejaud J, Lautram N, Dupont A, Eyer J

机构信息

Univ Angers, Inserm, CNRS, MINT, SFR ICAT, F-49000 Angers, France.

Univ Rennes, CNRS, Inserm, BIOSIT-UMS 3480, US_S 018 Rennes, France.

出版信息

Int J Pharm X. 2025 Aug 26;10:100382. doi: 10.1016/j.ijpx.2025.100382. eCollection 2025 Dec.

DOI:10.1016/j.ijpx.2025.100382
PMID:40933608
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12418994/
Abstract

Peptide conjugated-nanodrug is one of the most studied new treatment options in the field of cancer, including glioblastoma (GBM). This tumour, GBM, is a difficult to treat brain tumour mainly due to its location and the complexity of targeting tumour cells. A promising GBM-targeting peptide (NFL-TBS.40-63) is a cell penetrating peptide (CPP) that has previously demonstrated selectivity against GBM cells and also a capacity to damage their microtubule network at appropriate concentrations. Here, a potential nano-based delivery system was developed by coupling the biotinylated-NFL-peptide (BIOT-NFL) with lipid nanocapsules (LNCs) loaded with Colchicine (Col), an anti-microtubule agent with potent anticancer activity. The effect of BIOT-NFL and free Colchicine was first evaluated on GBM cells. Colchicine was then loaded in lipid nanocapsules (Col-loaded LNCs) and the obtained nanocapsules were characterized for particle size, morphology, encapsulation efficiency and release, and then coupled with the BIOT-NFL-peptide. Interestingly, a potential nanosystem composed of peptide-nanofibers (formed from BIOT-NFL) decorated with Col-LNCs was observed by electron microscopic examination. Finally, the effects of this BIOT-NFL coupled to Col-LNCs were evaluated on GBM cells. This new nanosystem may offer a promising strategy for GBM targeted therapy.

摘要

肽偶联纳米药物是癌症领域(包括胶质母细胞瘤,即GBM)研究最多的新型治疗选择之一。这种GBM肿瘤是一种难以治疗的脑肿瘤,主要是由于其位置以及靶向肿瘤细胞的复杂性。一种有前景的GBM靶向肽(NFL-TBS.40-63)是一种细胞穿透肽(CPP),它先前已证明对GBM细胞具有选择性,并且在适当浓度下能够破坏其微管网络。在此,通过将生物素化的NFL肽(BIOT-NFL)与负载秋水仙碱(Col)的脂质纳米胶囊(LNCs)偶联,开发了一种潜在的基于纳米的递送系统,秋水仙碱是一种具有强大抗癌活性的抗微管剂。首先评估了BIOT-NFL和游离秋水仙碱对GBM细胞的作用。然后将秋水仙碱负载到脂质纳米胶囊中(负载Col的LNCs),并对获得的纳米胶囊进行粒径、形态、包封率和释放特性的表征,然后与BIOT-NFL肽偶联。有趣的是,通过电子显微镜检查观察到了一种由用Col-LNCs修饰的肽纳米纤维(由BIOT-NFL形成)组成的潜在纳米系统。最后,评估了这种与Col-LNCs偶联的BIOT-NFL对GBM细胞的作用。这种新的纳米系统可能为GBM靶向治疗提供一种有前景的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04b/12418994/6254e522bffc/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04b/12418994/ce95ba8714c4/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04b/12418994/43f68db857be/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04b/12418994/0da746720eef/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04b/12418994/9473be945e7a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04b/12418994/d5d27327fa7e/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04b/12418994/9df7173f2d97/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04b/12418994/9f62ac738332/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04b/12418994/6254e522bffc/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04b/12418994/ce95ba8714c4/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04b/12418994/43f68db857be/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04b/12418994/0da746720eef/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04b/12418994/9473be945e7a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04b/12418994/d5d27327fa7e/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04b/12418994/9df7173f2d97/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04b/12418994/9f62ac738332/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d04b/12418994/6254e522bffc/gr7.jpg

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本文引用的文献

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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。
Int J Pharm. 2023 Nov 5;646:123421. doi: 10.1016/j.ijpharm.2023.123421. Epub 2023 Sep 16.
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Investigation on the self-assembly of the NFL-TBS.40-63 peptide and its interaction with gold nanoparticles as a delivery agent for glioblastoma.NFL-TBS.40-63肽的自组装及其作为胶质母细胞瘤递送剂与金纳米颗粒相互作用的研究
Int J Pharm X. 2022 Sep 22;4:100128. doi: 10.1016/j.ijpx.2022.100128. eCollection 2022 Dec.
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Characterization and quantification of the interaction between the NFL-TBS.40-63 peptide and lipid nanocapsules.
NFL-TBS.40-63 肽与脂质纳米囊泡之间相互作用的表征与定量分析
Int J Pharm X. 2022 Sep 16;4:100127. doi: 10.1016/j.ijpx.2022.100127. eCollection 2022 Dec.
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pH-Responsive Lipid Nanocapsules: A Promising Strategy for Improved Resistant Melanoma Cell Internalization.pH响应性脂质纳米胶囊:一种改善耐药黑色素瘤细胞内化的有前景策略。
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