Galloylated liposomes enable targeted drug delivery by overcoming protein corona shielding

Jinbo Li, Jiang Yu, Jia Song, Yingxi Zhang, Ning Li, Zhaomeng Wang, Meng Qin, Mingming Zhao, Baoyue Zhang, Ruiping Huang, Shuang Zhou, Yubo Liu, Zhonggui He, Hongzhuo Liu (), Liu () and Yongjun Wang ()
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Jinbo Li: Shenyang Pharmaceutical University
Jiang Yu: Shenyang Pharmaceutical University
Jia Song: Shenyang Pharmaceutical University
Yingxi Zhang: Shenyang Pharmaceutical University
Ning Li: Shenyang Pharmaceutical University
Zhaomeng Wang: Shengjing Hospital of China Medical University
Meng Qin: Shenyang Pharmaceutical University
Mingming Zhao: Shenyang Pharmaceutical University
Baoyue Zhang: Shenyang Pharmaceutical University
Ruiping Huang: Shenyang Pharmaceutical University
Shuang Zhou: Shenyang Pharmaceutical University
Yubo Liu: Shenyang Pharmaceutical University
Zhonggui He: Shenyang Pharmaceutical University
Hongzhuo Liu: Shenyang Pharmaceutical University
Liu: Shenyang Pharmaceutical University
Yongjun Wang: Shenyang Pharmaceutical University

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-63198-4

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