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Research Article

Engineering and preliminary evaluation of multiple non-equilibrium nanostructures from a single peptide amphiphile

Weiping Cui1,2,§Di Wu2,§Liuqing Yang2Chang Yang2Bing He2,3Hua Zhang2Xueqing Wang2Lei Zhang4( )Wenbing Dai2,3( )Qiang Zhang1,2,3( )
Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
Ningbo Institute of Marine Medicine, Peking University, Ningbo 315010, China
Electron Microscopy Analysis Laboratory, Medical and Health Analysis Center, Peking University, Beijing 100191, China

§ Weiping Cui and Di Wu contributed equally to this work.

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Graphical Abstract

The preparation methods of polymeric nanoparticles were creatively integrated into engineering non-equilibrium peptide assemblies, resulting in the generation of diverse non-equilibrium assemblies with multiple nanoarchitectures from a single peptide amphiphile. The non-equilibrium assemblies exhibited various degrees of bioactivities, which correlated with their dynamic transition behaviors.

Abstract

Compared with thermodynamically equilibrium supramolecular assemblies, non-equilibrium assemblies from the same building blocks have attracted increasing attentions because their diverse structures and dynamic natures may impart the assemblies with novel functionalities. However, facile access to non-equilibrium assemblies remains a formidable challenge. Herein, we endeavored to exploit various solvent-anti-solvent methods to achieve it using peptide amphiphile C16-VVAAEE-NH2 as a model. Through systematical utilization of dialysis, ultrasonic and stirring-dropping methods, as well as tuning of processing parameters, we demonstrated the successful formation of diverse non-equilibrium nanostructures with distinct morphologies and structures that significantly deviate from the thermodynamically favored twisted long ribbons. Additionally, these metastable nanostructures ultimately underwent spontaneous transformation into thermodynamically stable states. The transformation processes of three representative non-equilibrium assemblies were also demonstrated and characterized in detail using transmission electron microscopy, circular dichroism spectrum, and thioflavin T fluorescence spectrum. Furthermore, non-equilibrium assemblies exhibited various degrees of cytotoxic effects, which may stem from their spontaneous, dynamic transformation and interactions with cellular membranes. This study offers valuable approaches for direct access to diverse non-equilibrium supramolecular nanostructures from self-assembling peptide, and also has implications for the development of advanced materials with unprecedented biological functions.

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Nano Research
Pages 9764-9774
Cite this article:
Cui W, Wu D, Yang L, et al. Engineering and preliminary evaluation of multiple non-equilibrium nanostructures from a single peptide amphiphile. Nano Research, 2024, 17(11): 9764-9774. https://doi.org/10.1007/s12274-024-6960-3
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Received: 12 May 2024
Revised: 07 August 2024
Accepted: 11 August 2024
Published: 03 September 2024
© Tsinghua University Press 2024
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