Switchable supramolecular polycationic assemblies for tunable antibacterial strategies against antibiotic resistance

Jia Chen; Xueqian Wang; Mengrui Zhang; Xue Wang; Ran Wang; Xinxing Lyu; Yunjian Xu; Xintian Shao; Luling Wu; Tony D. James

doi:10.1039/d5sc05035a

Switchable supramolecular polycationic assemblies for tunable antibacterial strategies against antibiotic resistance

Jia Chen
, Xueqian Wang
, Mengrui Zhang
, Xue Wang
, Ran Wang
, Xinxing Lyu
, Yunjian Xu
, Xintian Shao
, Luling Wu
, Tony D. James

Shandong First Medical University & Shandong Academy of Medical Sciences
Nanjing University

Research output: Contribution to journal › Article › peer-review

1 Citation (SciVal)

Abstract

Bacterial resistance significantly hampers the efficacy of antibiotics in eradicating pathogens and treating infections. Here, we introduce an Adaptive Cationic Therapeutic Integrated (ACTI) system, a design strategy integrating pyridinium cationic membrane disruption and tunable antibacterial activity to address this challenge. ACTI leverages the assembled hyper-enriched cationic domains to enhance the destruction of bacterial membranes, while also enabling the on-demand deactivation of antibacterial activity through disassembly, thereby safeguarding biocompatibility. Additionally, ACTI facilitates the photodynamic inactivation of negatively charged photosensitizers (TPPS) by promoting the interaction between the photosensitizer and bacteria as well as aiding the transport of singlet oxygen. ACTI-loaded photosensitizers (TPPS@ACTI) exhibited potent antibacterial activity (>99% pathogen elimination) against methicillin-resistant S. aureus (MRSA) and E. coli in vitro, and the antibacterial efficacy was further validated using an MRSA-infected murine wound model. ACTI establishes a paradigm shift for the design of tunable antimicrobials that balance potency and biosafety in complex biological environments.

Original language	English
Pages (from-to)	20355-20367
Number of pages	13
Journal	Chemical Science
Volume	16
Issue number	43
Early online date	7 Oct 2025
DOIs	https://doi.org/10.1039/d5sc05035a
Publication status	Published - 21 Nov 2025

Data Availability Statement

Any other data that support the findings of this work are available from the corresponding author upon reasonable request.
All data of this work are provided in the article and as part of the supplementary information (SI). See DOI: https://doi.org/10.1039/d5sc05035a.

Acknowledgements

We used AI (ChatGPT) to help improve the English usage, then performed a final check and editing of the manuscript prior to submission.

Funding

This work was financially supported by the National Natural Science Foundation of China (no. 82302743 and 62205184) and Shandong Provincial Natural Science Foundation (ZR2025QC129). T. D. J. wishes to thank the University of Bath and the Open Research Fund of the School of Chemistry and Chemical Engineering, Henan Normal University (2020ZD01), for support. We used AI (ChatGPT) to help improve the English usage, then performed a final check and editing of the manuscript prior to submission.

Funders	Funder number
University of Bath
National Natural Science Foundation of China	62205184, 82302743
Natural Science Foundation of Shandong Province	ZR2025QC129
Henan Normal University	2020ZD01

ASJC Scopus subject areas

General Chemistry

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title = "Switchable supramolecular polycationic assemblies for tunable antibacterial strategies against antibiotic resistance",

abstract = "Bacterial resistance significantly hampers the efficacy of antibiotics in eradicating pathogens and treating infections. Here, we introduce an Adaptive Cationic Therapeutic Integrated (ACTI) system, a design strategy integrating pyridinium cationic membrane disruption and tunable antibacterial activity to address this challenge. ACTI leverages the assembled hyper-enriched cationic domains to enhance the destruction of bacterial membranes, while also enabling the on-demand deactivation of antibacterial activity through disassembly, thereby safeguarding biocompatibility. Additionally, ACTI facilitates the photodynamic inactivation of negatively charged photosensitizers (TPPS) by promoting the interaction between the photosensitizer and bacteria as well as aiding the transport of singlet oxygen. ACTI-loaded photosensitizers (TPPS@ACTI) exhibited potent antibacterial activity (>99\% pathogen elimination) against methicillin-resistant S. aureus (MRSA) and E. coli in vitro, and the antibacterial efficacy was further validated using an MRSA-infected murine wound model. ACTI establishes a paradigm shift for the design of tunable antimicrobials that balance potency and biosafety in complex biological environments.",

author = "Jia Chen and Xueqian Wang and Mengrui Zhang and Xue Wang and Ran Wang and Xinxing Lyu and Yunjian Xu and Xintian Shao and Luling Wu and James, \{Tony D.\}",

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AU - Chen, Jia

AU - Wang, Xueqian

AU - Zhang, Mengrui

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AU - Wang, Ran

AU - Lyu, Xinxing

AU - Xu, Yunjian

AU - Shao, Xintian

AU - Wu, Luling

AU - James, Tony D.

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N2 - Bacterial resistance significantly hampers the efficacy of antibiotics in eradicating pathogens and treating infections. Here, we introduce an Adaptive Cationic Therapeutic Integrated (ACTI) system, a design strategy integrating pyridinium cationic membrane disruption and tunable antibacterial activity to address this challenge. ACTI leverages the assembled hyper-enriched cationic domains to enhance the destruction of bacterial membranes, while also enabling the on-demand deactivation of antibacterial activity through disassembly, thereby safeguarding biocompatibility. Additionally, ACTI facilitates the photodynamic inactivation of negatively charged photosensitizers (TPPS) by promoting the interaction between the photosensitizer and bacteria as well as aiding the transport of singlet oxygen. ACTI-loaded photosensitizers (TPPS@ACTI) exhibited potent antibacterial activity (>99% pathogen elimination) against methicillin-resistant S. aureus (MRSA) and E. coli in vitro, and the antibacterial efficacy was further validated using an MRSA-infected murine wound model. ACTI establishes a paradigm shift for the design of tunable antimicrobials that balance potency and biosafety in complex biological environments.

AB - Bacterial resistance significantly hampers the efficacy of antibiotics in eradicating pathogens and treating infections. Here, we introduce an Adaptive Cationic Therapeutic Integrated (ACTI) system, a design strategy integrating pyridinium cationic membrane disruption and tunable antibacterial activity to address this challenge. ACTI leverages the assembled hyper-enriched cationic domains to enhance the destruction of bacterial membranes, while also enabling the on-demand deactivation of antibacterial activity through disassembly, thereby safeguarding biocompatibility. Additionally, ACTI facilitates the photodynamic inactivation of negatively charged photosensitizers (TPPS) by promoting the interaction between the photosensitizer and bacteria as well as aiding the transport of singlet oxygen. ACTI-loaded photosensitizers (TPPS@ACTI) exhibited potent antibacterial activity (>99% pathogen elimination) against methicillin-resistant S. aureus (MRSA) and E. coli in vitro, and the antibacterial efficacy was further validated using an MRSA-infected murine wound model. ACTI establishes a paradigm shift for the design of tunable antimicrobials that balance potency and biosafety in complex biological environments.

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Switchable supramolecular polycationic assemblies for tunable antibacterial strategies against antibiotic resistance

Abstract

Data Availability Statement

Acknowledgements

Funding

ASJC Scopus subject areas

Access to Document

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