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没食子酰化脂质体通过克服蛋白质冠层屏蔽实现靶向药物递送。

Galloylated liposomes enable targeted drug delivery by overcoming protein corona shielding.

作者信息

Li Jinbo, Yu Jiang, Song Jia, Zhang Yingxi, Li Ning, Wang Zhaomeng, Qin Meng, Zhao Mingming, Zhang Baoyue, Huang Ruiping, Zhou Shuang, Liu Yubo, He Zhonggui, Liu Hongzhuo, Wang Yongjun

机构信息

Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, China.

Department of Oncology, Cancer Stem Cell and Translational Medicine Lab, Innovative Cancer Drug Research and Development Engineering Center of Liaoning Province, Shengjing Hospital of China Medical University, Shenyang, China.

出版信息

Nat Commun. 2025 Aug 25;16(1):7926. doi: 10.1038/s41467-025-63198-4.


DOI:10.1038/s41467-025-63198-4
PMID:40854890
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12378351/
Abstract

Ligand-targeted nanomedicines provide precise delivery, enhance drug accumulation, and reduce side effects, but their clinical translation is hindered by challenges like protein corona formation, which can mask targeting ligands and impair functionality, and complex manufacturing processes. Here we develop galloylated liposomes (GA-lipo) by incorporating gallic acid-modified lipids into lipid bilayers, enabling the stable and controlled adsorption of targeting ligands through non-covalent physical interactions. This approach preserves ligand orientation and functionality, ensuring that binding sites remain exposed even in the presence of a protein corona. As a proof of concept, a weakly basic derivative of DXd (DXdd) is remotely loaded into liposomes, followed by trastuzumab adsorption, achieving 95% encapsulation efficiency for DXdd in 100 nm liposomes (with each trastuzumab molecule delivering approximately 580 DXdd molecules). These trastuzumab-functionalized immunoliposomes exhibit improved tumor inhibition in an SKOV3 tumor model, demonstrating the potential of GA-lipo as a simple and effective approach for constructing targeted nanomedicine delivery systems. This method overcomes key challenges in targeted drug delivery technologies, providing a scalable solution with broad clinical applicability.

摘要

配体靶向纳米药物可实现精准递送、增强药物积累并减少副作用,但其临床转化受到诸如蛋白质冠形成等挑战的阻碍,蛋白质冠会掩盖靶向配体并损害其功能,且制造过程复杂。在此,我们通过将没食子酸修饰的脂质掺入脂质双层来开发没食子酰化脂质体(GA-脂质体),通过非共价物理相互作用实现靶向配体的稳定且可控吸附。这种方法保留了配体的方向和功能,确保即使在存在蛋白质冠的情况下结合位点仍保持暴露。作为概念验证,将DXd的弱碱性衍生物(DXdd)远程载入脂质体,随后吸附曲妥珠单抗,在100 nm脂质体中DXdd的包封效率达到95%(每个曲妥珠单抗分子递送约580个DXdd分子)。这些曲妥珠单抗功能化的免疫脂质体在SKOV3肿瘤模型中表现出更好的肿瘤抑制效果,证明了GA-脂质体作为构建靶向纳米药物递送系统的简单有效方法的潜力。该方法克服了靶向药物递送技术中的关键挑战,提供了一种具有广泛临床适用性的可扩展解决方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adf4/12378351/4d5b114042a2/41467_2025_63198_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adf4/12378351/e06753d69551/41467_2025_63198_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adf4/12378351/ad235fb8a0e3/41467_2025_63198_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adf4/12378351/fdf86affbbe4/41467_2025_63198_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adf4/12378351/3e183292f2b9/41467_2025_63198_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adf4/12378351/c65242f0b312/41467_2025_63198_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adf4/12378351/4d5b114042a2/41467_2025_63198_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adf4/12378351/e06753d69551/41467_2025_63198_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adf4/12378351/ad235fb8a0e3/41467_2025_63198_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adf4/12378351/fdf86affbbe4/41467_2025_63198_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adf4/12378351/3e183292f2b9/41467_2025_63198_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adf4/12378351/c65242f0b312/41467_2025_63198_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adf4/12378351/4d5b114042a2/41467_2025_63198_Fig6_HTML.jpg

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[1]
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本文引用的文献

[1]
Rational design of DXd derivatives for liposomal drug delivery: Towards safer and more effective cancer treatments.

Int J Pharm. 2025-6-10

[2]
Cancer therapy with antibodies.

Nat Rev Cancer. 2024-6

[3]
High-Throughput Host-Microbe Single-Cell RNA Sequencing Reveals Ferroptosis-Associated Heterogeneity during Acinetobacter baumannii Infection.

Angew Chem Int Ed Engl. 2024-4-24

[4]
Controlled adsorption of multiple bioactive proteins enables targeted mast cell nanotherapy.

Nat Nanotechnol. 2024-5

[5]
Exploring the next generation of antibody-drug conjugates.

Nat Rev Clin Oncol. 2024-3

[6]
The protein corona from nanomedicine to environmental science.

Nat Rev Mater. 2023-3-24

[7]
The role of protein corona on nanodrugs for organ-targeting and its prospects of application.

J Control Release. 2023-8

[8]
Targeted nanomedicine: Lessons learned and future directions.

J Control Release. 2023-3

[9]
Bioinspired Nanocomplexes Comprising Phenolic Acid Derivative and Human Serum Albumin for Cancer Therapy.

Nano Lett. 2022-12-28

[10]
Antibody-Incorporated Nanomedicines for Cancer Therapy.

Adv Mater. 2022-6

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