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研究肽核酸与多组分肽水凝胶的相互作用以推动医疗技术发展。

Investigating the Interactions of Peptide Nucleic Acids with Multicomponent Peptide Hydrogels for the Advancement of Healthcare Technologies.

作者信息

Giordano Sabrina, Terracciano Monica, Gallo Enrico, Diaferia Carlo, Falanga Andrea Patrizia, Accardo Antonella, Franzese Monica, Salvatore Marco, Piccialli Gennaro, Borbone Nicola, Oliviero Giorgia

机构信息

IRCCS SYNLAB SDN, Via G. Ferraris 144, 80143 Naples, Italy.

Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131 Naples, Italy.

出版信息

Gels. 2025 May 17;11(5):367. doi: 10.3390/gels11050367.

DOI:10.3390/gels11050367
PMID:40422386
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12111274/
Abstract

This study reports the development of peptide-based hydrogels for the encapsulation and controlled release of peptide nucleic acids in drug delivery applications. Ultrashort aromatic peptides, such as Fmoc-FF, self-assemble into biocompatible hydrogels with nanostructured architectures. The functionalization of tripeptides (Fmoc-FFK and Fmoc-FFC) with lysine (K) or cysteine (C) enables electrostatic or covalent interactions with model PNAs engineered with glutamic acid or cysteine residues, respectively. Hydrogels were polymerized in situ in the presence of PNAs, and component ratios were systematically varied to optimize mechanical properties, loading efficiency, and release kinetics. The formulations obtained with a 1/10 ratio of Fmoc-FF(K or C)/Fmoc-FF provided an optimal balance between structural integrity and delivery performance. All hydrogel formulations demonstrated high stiffness (G' > 19,000 Pa), excellent water retention, and minimal swelling under physiological conditions (ΔW < 4%). The release studies over 10 days showed that electrostatic loading enabled faster and higher release (up to 90%), while covalent bonding resulted in slower, sustained delivery (~15%). These findings highlight the tunability of the hydrogel system for diverse therapeutic applications.

摘要

本研究报道了用于药物递送应用中肽核酸包封和控释的基于肽的水凝胶的开发。超短芳香肽，如Fmoc-FF，自组装成具有纳米结构的生物相容性水凝胶。用赖氨酸（K）或半胱氨酸（C）对三肽（Fmoc-FFK和Fmoc-FFC）进行功能化，分别实现与用谷氨酸或半胱氨酸残基设计的模型肽核酸的静电或共价相互作用。水凝胶在肽核酸存在下原位聚合，并系统地改变组分比例以优化机械性能、负载效率和释放动力学。以Fmoc-FF（K或C）/Fmoc-FF 1/10的比例获得的制剂在结构完整性和递送性能之间提供了最佳平衡。所有水凝胶制剂在生理条件下均表现出高刚度（G' > 19,000 Pa）、优异的保水性和最小的溶胀（ΔW < 4%）。超过10天的释放研究表明，静电负载能够实现更快、更高的释放（高达90%），而共价键合导致更慢、持续的递送（约15%）。这些发现突出了水凝胶系统在多种治疗应用中的可调性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8116/12111274/ceee9be06e26/gels-11-00367-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8116/12111274/0a175e4a1597/gels-11-00367-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8116/12111274/97a3ed38e081/gels-11-00367-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8116/12111274/8583faa05177/gels-11-00367-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8116/12111274/dab1a758b379/gels-11-00367-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8116/12111274/cf322a7ca08f/gels-11-00367-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8116/12111274/da803bdd5e13/gels-11-00367-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8116/12111274/b52bdee46ea3/gels-11-00367-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8116/12111274/d4efbd97f1ab/gels-11-00367-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8116/12111274/ceee9be06e26/gels-11-00367-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8116/12111274/0a175e4a1597/gels-11-00367-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8116/12111274/97a3ed38e081/gels-11-00367-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8116/12111274/8583faa05177/gels-11-00367-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8116/12111274/dab1a758b379/gels-11-00367-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8116/12111274/cf322a7ca08f/gels-11-00367-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8116/12111274/da803bdd5e13/gels-11-00367-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8116/12111274/b52bdee46ea3/gels-11-00367-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8116/12111274/d4efbd97f1ab/gels-11-00367-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8116/12111274/ceee9be06e26/gels-11-00367-g009.jpg

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Peptide nucleic acids: Recent advancements and future opportunities in biomedical applications.肽核酸：生物医学应用中的最新进展与未来机遇
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