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journal article·2025-11Open access

A Lipid with Lewis Pair‐Mediated Targeting and Multiple Stimuli‐Responsive Delivery of Antibiotics for Bacterial Infections

Xiaojian Yan, Lei Hua, Hongping Wan, Yong Liu, Tao Jin, Yicen Ge, Michael R Hamblin, Mahdi Karimi, Xinghong Zhao, Yan Hu, Linqi Shi, Yuanfeng Li

Advanced Science· Volume 12· Issue 43
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Source abstract

Abstract

Abstract Integrating both targeted delivery and stimulus‐responsive release into a single small molecule for drug delivery presents challenges related to synthesis, stability, and efficacy. In this study, single‐molecular lipids incorporating a Lewis pair ( Lp ‐lipids) are described, composed of a Lewis acid (phenylboronic acid) and a Lewis base (amine) within a single small molecular structure, to formulate lipid nanoparticles for antibiotic delivery. For targeted delivery to bacterial biofilms, the phenylboronic acid selectively binds to bacteria or biofilms by forming boronate ester bonds with diols in the microbial dextran or peptidoglycan. Additionally, the amine group responds to the acidic microenvironment, enhancing electrostatic interactions with bacteria and biofilms. Regarding stimulus‐responsive drug release, the Lewis base reacts to low pH, while the Lewis acid responds to H 2 O 2 and ATP, triggering changes in the hydrophobicity and structural integrity of the lipid nanoparticles. These changes facilitate the release of encapsulated antibiotics, effectively eradicating both Gram‐positive and Gram‐negative bacteria in vitro and in vivo. The combined targeting and stimuli‐responsive release properties of Lp ‐lipids significantly enhance their potential for biomedical applications and clinical translation.
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Research context

Nanomaterials

OpenAlex topics: Lipid Membrane Structure and Behavior · Nanoparticle-Based Drug Delivery · Advanced Drug Delivery Systems

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation Department of Gynecology Consortium for Infection and Innovation (CII) First Affiliated Hospital Wenzhou Medical University Wenzhou 325035 China

Wenzhou Institute University of the Chinese Academy of Sciences Wenzhou Zhejiang 325001 China

Center for Sustainable Antimicrobials Center for Infectious Diseases Control (CIDC) Department of Pharmacy College of Veterinary Medicine Sichuan Agricultural University Chengdu 611130 China

Translational Medicine Laboratory The First Affiliated Hospital of Wenzhou Medical University Wenzhou Medical University Wenzhou Zhejiang 325001 China

State Key Laboratory of Medicinal Chemical Biology Nankai University Tianjin 300071 China

College of Materials Chemistry and Chemical Engineering Chengdu University of Technology Chengdu Sichuan 610059 China

Laser Research Centre University of Johannesburg Doornfontein Johannesburg 2028 South Africa

Cellular and Molecular Research Center Iran University of Medical Sciences Tehran 14535 Iran

Funding

National Natural Science Foundation of China

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