Fluorescence of Aggregated Aromatic Peptides for Studying the Kinetics of Aggregation and Hardening of Amyloid-like Structures.

The capability of amyloid-like peptide fibers to emit intrinsic-fluorescence enables the study of their formation, stability and hardening through time-resolved fluorescence analysis, without the need for additional intercalating dyes. This approach allows the monitoring of amyloid-like peptides aggregation kinetics using minimal sample volumes, and the simultaneous testing of numerous experimental conditions and analytes, offering rapid and reproducible results. The analytical procedure applied to the aromatic hexapeptide F6, alone or derivatized with PEG (polyethylene glycol) moiety of different lengths, suggests that aggregation into large anisotropic structures negatively correlates with initial monomer concentration and relies on the presence of charged N- and C-termini.

Hybrid PNA-peptide hydrogels as injectable CEST-MRI agents.

The self-assembly of peptides and peptide analogues may be exploited to develop platforms for different biomedical applications, among which CEST-MRI (chemical exchange saturation transfer magnetic resonance imaging) represents one of the most attractive techniques to be explored as a novel metal-free contrast approach in imaging acquisitions. A lysine-containing peptide sequence (LIVAGK-NH, named K2) was thus modified by insertion, at the N-terminus, of a peptide nucleic acid (PNA) base, leading to a primary amine suitable for the signal generation. a-K2, c-K2, g-K2 and t-K2 peptides were synthesized and characterized.

Fmoc-FF hydrogels and nanogels for improved and selective delivery of dexamethasone in leukemic cells and diagnostic applications.

Dexamethasone (DEX) is a synthetic analogue of cortisol commonly used for the treatment of different pathological conditions, comprising cancer, ocular disorders, and COVID-19 infection. Its clinical use is hampered by the low solubility and severe side effects due to its systemic administration. The capability of peptide-based nanosystems, like hydrogels (HGs) and nanogels (NGs), to serve as vehicles for the passive targeting of active pharmaceutical ingredients and the selective internalization into leukemic cells has here been demonstrated.

Ultrashort Cationic Peptide Fmoc-FFK as Hydrogel Building Block for Potential Biomedical Applications.

Fmoc-diphenylalanine (Fmoc-FF) is a low-molecular-weight peptide hydrogelator. This simple all-aromatic peptide can generate self-supporting hydrogel materials, which have been proposed as novel materials for diagnostic and pharmaceutical applications. Our knowledge of the molecular determinants of Fmoc-FF aggregation is used as a guide to design new peptide-based gelators, with features for the development of improved tools.

Multicomponent Peptide-Based Hydrogels Containing Chemical Functional Groups as Innovative Platforms for Biotechnological Applications.

Multicomponent hydrogels (HGs) based on ultrashort aromatic peptides have been exploited as biocompatible matrices for tissue engineering applications, the delivery of therapeutic and diagnostic agents, and the development of biosensors. Due to its capability to gel under physiological conditions of pH and ionic strength, the low molecular-weight Fmoc-FF (N-fluorenylmethoxycarbonyl-diphenylalanine) homodimer is one of the most studied hydrogelators. The introduction into the Fmoc-FF hydrogel of additional molecules like protein, organic compounds, or other peptide sequences often allows the generation of novel hydrogels with improved mechanical and functional properties.

Development of cationic peptide-based hydrogels loaded with iopamidol for CEST-MRI detection.

Peptide-based hydrogels have been recently investigated as materials for biomedical applications like tissue engineering and delivery of drugs and imaging agents. Among the synthetic peptide hydrogelators, the cationic hexapeptides Ac-K1 and Ac-K2 were proposed as scaffolds for bioprinting applications. Here, we report the formulation of Ac-K1 and Ac-K2 hydrogels loaded with iopamidol, an iodinated contrast agent clinically approved for X-ray computed tomography, and more recently identified as an efficient CEST-MRI probe.

Caveolin-Mediated Internalization of Fmoc-FF Nanogels in Breast Cancer Cell Lines.

Hydrogel nanoparticles, also known as nanogels (NGs), have been recently proposed as alternative supramolecular vehicles for the delivery of biologically relevant molecules like anticancer drugs and contrast agents. The inner compartment of peptide based NGs can be opportunely modified according to the chemical features of the cargo, thus improving its loading and release. A full understanding of the intracellular mechanism involved in nanogel uptake by cancer cells and tissues would further contribute to the potential diagnostic and clinical applications of these nanocarriers, allowing the fine tuning of their selectivity, potency, and activity.

Incorporation of PEG Diacrylates (PEGDA) Generates Hybrid Fmoc-FF Hydrogel Matrices.

Generated by a hierarchical and multiscale self-assembling phenomenon, peptide-based hydrogels (HGs) are soft materials useful for a variety of applications. Short and ultra-short peptides are intriguing building blocks for hydrogel fabrication. These matrices can also be obtained by mixing low-molecular-weight peptides with other chemical entities (e.

Multicomponent Hydrogel Matrices of Fmoc-FF and Cationic Peptides for Application in Tissue Engineering.

In the last years, peptide-based hydrogels are being increasingly used as suitable matrices for biomedical and pharmaceutical applications, including drug delivery and tissue engineering. Recently, the synthesis and the gelation properties of a small library of cationic peptides, containing a Lys residue at the C-terminus and derivatized with an Fmoc group or with the fluorenyl methoxycarbonyl-diphenylalanine (FmocFF) at the N-terminus are derived. Here, it is demonstrated that the combination of these peptides with the well-known hydrogelator FmocFF, in different weight/weight ratios, allows the achievement of seven novel self-sorted hydrogels, which share similar peptide organization of their supramolecular matrix.

Comparative Proteomic Profiling of Secreted Extracellular Vesicles from Breast Fibroadenoma and Malignant Lesions: A Pilot Study.

Extracellular vesicles (EVs) shuttle proteins, RNA, DNA, and lipids crucial for cell-to-cell communication. Recent findings have highlighted that EVs, by virtue of their cargo, may also contribute to breast cancer (BC) growth and metastatic dissemination. Indeed, EVs are gaining great interest as non-invasive cancer biomarkers.

Solid-state optical properties of self-assembling amyloid-like peptides with different charged states at the terminal ends.

The self-assembling of small peptides not only leads to the formation of intriguing nanoarchitectures, but also generates materials with unexpected functional properties. Oligopeptides can form amyloid-like cross-β assemblies that are able to emit intrinsic photoluminescence (PL), over the whole near-UV/visible range, whose origin is still largely debated. As proton transfer between the peptide chain termini within the assembly is one of the invoked interpretations of this phenomenon, we here evaluated the solid state PL properties of a series of self-assembled hexaphenylalanine peptides characterized by a different terminal charge state.

Fluorescence Emission of Self-assembling Amyloid-like Peptides: Solution versus Solid State.

Analysis of the intrinsic UV-visible fluorescence exhibited by self-assembling amyloid-like peptides in solution and in solid the state highlights that their physical state has a profound impact on the optical properties. In the solid state, a linear dependence of the fluorescence emission peaks as a function of excitation wavelength is detected. On the contrary, an excitation-independent emission is observed in solution.

Diphenylalanine Motif Drives Self-Assembling in Hybrid PNA-Peptide Conjugates.

Peptides and nucleic acids can self-assemble to give supramolecular structures that find application in different fields, ranging from the delivery of drugs to the obtainment of materials endowed with optical properties. Forces that stabilize the "suprastructures" typically are hydrogen bonds or aromatic interactions; in case of nucleic acids, Watson-Crick pairing drives self-assembly while, in case of peptides, backbone hydrogen bonds and interactions between aromatic side chains trigger the formation of structures, such as nanotubes or ribbons. Molecules containing both aromatic peptides and nucleic acids could in principle exploit different forces to self-assemble.

Self-Supporting Hydrogels Based on Fmoc-Derivatized Cationic Hexapeptides for Potential Biomedical Applications.

Peptide-based hydrogels (PHGs) are biocompatible materials suitable for biological, biomedical, and biotechnological applications, such as drug delivery and diagnostic tools for imaging. Recently, a novel class of synthetic hydrogel-forming amphiphilic cationic peptides (referred to as series K), containing an aliphatic region and a Lys residue, was proposed as a scaffold for bioprinting applications. Here, we report the synthesis of six analogues of the series K, in which the acetyl group at the N-terminus is replaced by aromatic portions, such as the Fmoc protecting group or the Fmoc-FF hydrogelator.

Peptide-Based Hydrogels and Nanogels for Delivery of Doxorubicin.

Introduction: The clinical use of the antitumoral drug doxorubicin (Dox) is reduced by its dose-limiting toxicity, related to cardiotoxic side effects and myelosuppression. In order to overcome these drawbacks, here we describe the synthesis, the structural characterization and the in vitro cytotoxicity assays of hydrogels (HGs) and nanogels (NGs) based on short peptide sequences loaded with Dox or with its liposomal formulation, Doxil.

Methods: Fmoc-FF alone or in combination with (FY)3 or PEG8-(FY)3 peptides, at two different ratios (1/1 and 2/1 v/v), were used for HGs and NGs formulations.

Fabrication of fluorescent nanospheres by heating PEGylated tetratyrosine nanofibers.

Aromatic polypeptides have recently drawn the interest of the research community for their capability to self-assemble into a variety of functional nanostructures. Due to their interesting mechanical, electrical and optical properties, these nanostructures have been proposed as innovative materials in different biomedical, biotechnological and industrial fields. Recently, several efforts have been employed in the development of these innovative materials as nanoscale fluorescence (FL) imaging probes.

Stable Formulations of Peptide-Based Nanogels.

Recently, nanogels have been identified as innovative formulations for enlarging the application of hydrogels (HGs) in the area of drug delivery or in diagnostic imaging. Nanogels are HGs-based aggregates with sizes in the range of nanometers and formulated in order to obtain injectable preparations. Regardless of the advantages offered by peptides in a hydrogel preparation, until now, only a few examples of peptide-based nanogels (PBNs) have been developed.

Systematic overview of soft materials as a novel frontier for MRI contrast agents.

Magnetic resonance imaging (MRI) is a well-known diagnostic technique used to obtain high quality images in a non-invasive manner. In order to increase the contrast between normal and pathological regions in the human body, positive (T1) or negative (T2) contrast agents (CAs) are commonly intravenously administered. The most efficient class of T1-CAs are based on kinetically stable and thermodynamically inert gadolinium complexes.

Peptide-Based Soft Hydrogels Modified with Gadolinium Complexes as MRI Contrast Agents.

Poly-aromatic peptide sequences are able to self-assemble into a variety of supramolecular aggregates such as fibers, hydrogels, and tree-like multi-branched nanostructures. Due to their biocompatible nature, these peptide nanostructures have been proposed for several applications in biology and nanomedicine (tissue engineering, drug delivery, bioimaging, and fabrication of biosensors). Here we report the synthesis, the structural characterization and the relaxometric behavior of two novel supramolecular diagnostic agents for magnetic resonance imaging (MRI) technique.

Fmoc-FF and hexapeptide-based multicomponent hydrogels as scaffold materials.

Short peptides or single amino acids are interesting building blocks for fabrication of hydrogels, frequently used as extracellular matrix-mimicking scaffolds for cell growth in tissue engineering. The combination of two or more peptide hydrogelators could allow obtaining different materials exhibiting new architectures, tunable mechanical properties, high stability and improved biofunctionality. Here we report on the synthesis, formulation and multi-scale characterization of peptide-based mixed hydrogels formed by the low molecular weight Fmoc-FF (N-fluorenylmethyloxycarbonyl diphenylalanine) hydrogelator and of the PEG-(FY)3 hexapeptide, containing three repetitions of the Phe-Tyr motif and a PEG moiety at its N-terminus.

Assembly modes of hexaphenylalanine variants as function of the charge states of their terminal ends.

The ability of peptides to self-assemble represents a valuable tool for the development of biomaterials of biotechnological and/or biomedical interest. Diphenylalanine homodimer (FF) and its analogues are among the most promising systems in this field. The longest Phe-based building block hitherto characterized is pentaphenylalanine (F5).