Jervis Peter J, Hilliou Loic, Pereira Renato B, Pereira David M, Martins José A, Ferreira Paula M T
Center of Chemistry, University of Minho, 4710-057 Braga, Portugal.
Institute for Polymers and Composites, University of Minho, 4800-058 Guimarães, Portugal.
Nanomaterials (Basel). 2021 Mar 11;11(3):704. doi: 10.3390/nano11030704.
Short peptides capped on the -terminus with aromatic groups are often able to form supramolecular hydrogels, via self-assembly, in aqueous media. The rheological properties of these readily tunable hydrogels resemble those of the extracellular matrix (ECM) and therefore have potential for various biological applications, such as tissue engineering, biosensors, 3D bioprinting, drug delivery systems and wound dressings. We herein report a new photo-responsive supramolecular hydrogel based on a "caged" dehydropeptide (CNB-Phe-ΔPhe-OH ), containing a photo-cleavable carboxy-2-nitrobenzyl (CNB) group. We have characterized this hydrogel using a range of techniques. Irradiation with UV light cleaves the pendant aromatic capping group, to liberate the corresponding uncaged model dehydropeptide (H-Phe-ΔPhe-OH ), a process which was investigated by H NMR and HPLC studies. Crucially, this cleavage of the capping group is accompanied by dissolution of the hydrogel (studied visually and by fluorescence spectroscopy), as the delicate balance of intramolecular interactions within the hydrogel structure is disrupted. Hydrogels which can be disassembled non-invasively with temporal and spatial control have great potential for specialized on-demand drug release systems, wound dressing materials and various topical treatments. Both and were found to be non-cytotoxic to the human keratinocyte cell line, HaCaT. The UV-responsive hydrogel system reported here is complementary to previously reported related UV-responsive systems, which are generally composed of peptides formed from canonical amino acids, which are susceptible to enzymatic proteolysis in vivo. This system is based on a dehydrodipeptide structure which is known to confer proteolytic resistance. We have investigated the ability of the photo-activated system to accelerate the release of the antibiotic, ciprofloxacin, as well as some other small model drug compounds. We have also conducted some initial studies towards skin-related applications. Moreover, this model system could potentially be adapted for on-demand "self-delivery", through the uncaging of known biologically active dehydrodipeptides.
在α-末端带有芳香基团的短肽通常能够在水性介质中通过自组装形成超分子水凝胶。这些易于调节的水凝胶的流变学性质类似于细胞外基质（ECM），因此在各种生物应用中具有潜力，如组织工程、生物传感器、3D生物打印、药物递送系统和伤口敷料。我们在此报告一种基于“笼形”脱氢肽（CNB-Phe-ΔPhe-OH）的新型光响应超分子水凝胶，其含有可光裂解的羧基-2-硝基苄基（CNB）基团。我们使用一系列技术对这种水凝胶进行了表征。用紫外光照射会裂解侧链芳香封端基团，以释放相应的未笼形模型脱氢肽（H-Phe-ΔPhe-OH），这一过程通过1H NMR和HPLC研究进行了探究。至关重要的是，封端基团的这种裂解伴随着水凝胶的溶解（通过肉眼观察和荧光光谱研究），因为水凝胶结构内部分子间相互作用的微妙平衡被打破。能够通过时间和空间控制进行非侵入性拆解的水凝胶在专门的按需药物释放系统、伤口敷料材料和各种局部治疗中具有巨大潜力。发现两者对人角质形成细胞系HaCaT均无细胞毒性。此处报道的紫外响应水凝胶系统与先前报道的相关紫外响应系统互补，后者通常由由标准氨基酸形成的肽组成，在体内易受酶促蛋白水解作用。该系统基于已知具有蛋白水解抗性的脱氢二肽结构。我们研究了光激活系统加速抗生素环丙沙星以及其他一些小模型药物化合物释放的能力。我们还针对与皮肤相关的应用进行了一些初步研究。此外，通过解开已知的生物活性脱氢二肽的笼形，该模型系统可能适用于按需“自递送”。
