Anna Mitraki

Copper and zinc nanoparticles have been suggested as potent anticancer agents, particularly against osteosarcoma, a highly aggressive bone cancer with limited treatment options. In order to avoid systemic toxicity, biomolecular carriers able to chelate metal ions and deliver them in a targeted manner to the vicinity of cancer cells need to be developed. Herein, we have used a histidine-containing, cyclic dipeptide as a carrier able to chelate stabilized copper and zinc nanoparticles. The cyclic peptide cyclo-(histidine-phenylalanine) (cHF) self-assembled into amyloid-type fibrils; morphological and structural characterization following metal addition confirmed the formation of cHF−CuNPs and cHF–ZnNPs. These composite nanoparticles demonstrated bacteriostatic activity against Escherichia coli and Staphylococcus aureus at the in vitro level. We evaluated the optimal concentration of cHF–metalNP complexes with limited cytotoxicity to L929 fibroblasts and high cytotoxic effects against MG-63 osteosarcoma cells. Their cytotoxicity was particularly pronounced at pH 6.4, which emulates the tumor microenvironment. The cHF peptide alone did not demonstrate significant antimicrobial or cytotoxic effects to both cell types, suggesting that it can act as a cytocompatible, pH-responsive carrier of metal ions with targeted dual functionality against both microbial infections and osteosarcoma cancer cells.

Two-photon polymerization (2PP) enables the fabrication of complex 3D scaffolds for tissue engineering, yet the lack of biocompatible and bioactive photoinitiators remains a bottleneck for functional bio-manufacturing. Here, a one-step strategy is presented using curcumin (CUR), a naturally derived polyphenol, as a high-efficiency multifunctional photoinitiator for gelatin methacryloyl (GelMA) hydrogels. Nonlinear optical characterization reveals a synergistic interaction between CUR and the GelMA protein backbone, resulting in a significantly enhanced two-photon absorption cross-section (σ ≈ 1500 GM) that outperforms conventional initiators. This synergy facilitates an exceptionally broad processing window and high-speed fabrication (up to 52 mm/s) of high-fidelity, complex triply periodic minimal surface (TPMS) and biomimetic bone-like scaffolds. Beyond its initiation efficiency, CUR imparts intrinsic multifunctionality to the resulting 3D constructs. The scaffolds exhibit exceptional biocompatibility with mesenchymal stem cells while demonstrating a potent dual-action antimicrobial defense: a selective passive antifouling effect against E. coli and active photodynamic eradication (>99.9%) of S. aureus upon blue LED irradiation. This "all-in-one" approach transforms the photoinitiator from an inert processing tool into a source of intrinsic scaffold bioactivity, eliminating the need for complex post-fabrication functionalization.

Emerging neurotrophin treatments for optic nerve injury (ONI) aim to prevent the loss of retinal ganglion cells (RGCs) and enhance axonal regeneration. Microneurotrophins (MNTs), small‐molecule mimetics of neurotrophins, have shown neuroprotective effects in various animal models of neurodegeneration, yet MNT effects on ONI remain unknown. Here, we study the effects of BNN27, a MNT that mimics NGF, in a mouse model of optic nerve crush (ONC) and compare the targeted administration via biomaterial grafts placed around the ONC lesion against standard eye drop delivery. Compared to eye drop delivery, targeted biomaterial‐based BNN27 delivery resulted in more consistent and efficient RGC neuroprotection and reduced microglia‐mediated inflammation in the ONC lesion. Our findings demonstrate that targeted delivery of MNTs can alleviate key consequences of ONI and, therefore, be an essential part of effective combinatorial ONI treatments.

Herein, it is reported the visible‐light‐induced green hydrogen generation from self‐assembled porphyrin‐dipeptide hybrids. For the first time the self‐assembly ability of a protected alanine‐phenylalanine dipeptide is investigated via a simple protocol, which proved efficient in forming well‐defined fibrillar architectures. These self‐assembling properties are conveyed to peptide‐porphyrin chromophores after their covalent conjugation. Interestingly, different architectures are observed depending on the solvent system, the solvent evaporation rate, the presence of metal in the porphyrin core, and the peripheral substitution of the porphyrin. Moving one step forward, it is explored the activity of the self‐assembled nanostructures towards photocatalytic green H ₂ production from aqueous protons under visible‐light irradiation. The distinct self‐assembly behavior of the synthesized conjugates and their impact on photocatalytic hydrogen production is systematically explored in this study. Nonlinear second harmonic generation optical measurements are employed to define how the shape of the nanostructures is related to the H ₂ production efficiency. Notably, the tubular nanostructures presented the best catalytic performance, achieving a high H ₂ production activity of 32.7 mmol·g ⁻¹ ·h ⁻¹ . Through detailed characterization and performance evaluation, it is aimed to uncover new insights into the design and optimization of peptide‐porphyrin‐based photocatalysts for sustainable energy applications.

One major public health issue is cancer chemotherapy; despite constant progress in the area, administration of anticancer drugs to patients is often associated with serious side effects. It is therefore imperative to develop vehicles for encapsulation and controlled delivery of such drugs. Anticancer drugs include small peptide drugs, such as Bortezomib (BTZ). Self-assembling peptides have been recently reported as promising drug delivery agents. The research reported here proposes the encapsulation of BTZ into peptide hydrogels formed by the self-assembling FmocFF dipeptide as delivery vehicle. We selected FmocFF as an encapsulation vehicle based on our previous simulation study on the complexation propensity of Bortezomib (BTZ) with various peptide gelators. Herein we undertook additional computational studies that highlight the benefits of FmocFF as a potential effective nanocarrier for BTZ combined with experiments of encapsulation and evaluation of BTZ release. Based on these computational and experimental results, we propose the Fmoc-FF dipeptide hydrogel as a promising matrix for the controlled delivery of BTZ.

Antimicrobial resistance (AMR) poses a significant global health risk as a consequence of misuse of antibiotics. Owing to the increasing antimicrobial resistance, it became imperative to develop novel molecules and materials with antimicrobial properties. Porphyrins and metalloporphyrins are compounds which present antimicrobial properties especially after irradiation. As a consequence, porphyrinoids have recently been utilized as antimicrobial agents in antimicrobial photodynamic inactivation in bacteria and other microorganisms. Herein, we report the encapsulation of porphyrins into peptide hydrogels which serve as delivery vehicles. We selected the self-assembling Fmoc-Phe-Phe dipeptide, a potent gelator, as a scaffold due to its previously reported biocompatibility and three different water-soluble porphyrins as photosensitizers. We evaluated the structural, mechanical and in vitro degradation properties of these hydrogels, their interaction with NIH3T3 mouse skin fibroblasts, and we assessed their antimicrobial efficacy against Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) bacteria. We found out that the hydrogels are cytocompatible and display antimicrobial efficiency against both strains with the zinc porphyrins being more efficient. Therefore, these hydrogels present a promising alternative for combating bacterial infections in the face of growing AMR concerns.

The investigation of potential self-assembled peptides as carriers for the delivery of anticancer drug Bortezomib is the topic of the present study.

Self-assembling dipeptides have emerged in the last two decades as promising building blocks for the development of novel biomaterials. Among the various classes of dipeptides, aromatic dipeptides and especially diphenylalanine (Phe–Phe), which forms hexagonal nanotubes, have been the most extensively studied. However, aliphatic peptides or mixed aromatic–aliphatic dipeptides seem just as promising, exhibiting various structures ranging from amyloid fibrils to microtubes. Herein we report the single-crystal structure of an aliphatic dipeptide, alanine–isoleucine (Ala–Ile), C₁₇H₂₄N₂O₅, protected with a benzyloxycarbonyl (Z) group at the N-terminus. The protected dipeptide crystallizes in the orthorhombic space group P2₁2₁2₁ and forms hollow microtubes with orthorhombic symmetry upon evaporation on glass surfaces, as shown by field emission scanning electron microscopy (FESEM). These findings provide an increased understanding of the correlation between the single-crystal structure of the peptide building block and its self-assembly mechanism, and expand the library of available building blocks for microtechnological applications.

For over two decades, peptide self-assembly has been the focus of attention and a great source of inspiration for biomedical and nanotechnological applications. The resulting peptide nanostructures and their properties are closely related to the information encoded within each peptide building block, their sequence, and their modes of self-organization. In this work. we assess the behavior and differences between the self-association of the aromatic-aliphatic Phe-Leu dipeptide compared to its retro-sequence Leu-Phe and cyclic Cyclo(-Leu-Phe) counterparts, using a combination of simulation and experimental methods. Detailed all-atom molecular dynamics (MD) simulations offer a quantitative prediction at the molecular level of the conformational, dynamical and structural properties of the peptides' self-assembly, while field emission scanning electron microscopy (FESEM) experiments allow microscopic observation of the self-assembled end-structures. The complementarity and qualitative agreement between the two methods not only highlights the differences between the self-assembly propensity of cyclic and linear retro-sequence peptides but also sheds light on underlying mechanisms of self-organization. The self-assembling propensity was found to follow the order: Cyclo(-Leu-Phe) > Leu-Phe > Phe-Leu.

There is a growing concern about wound care, since traditional dressings such as bandages and sutures can no longer meet existing needs. To address the demanding requirements, naturally occurring polymers have been extensively exploited for use in modern wound management. Polysaccharides, being the most abundant biopolymers, have some distinct characteristics, including biocompatibility and biodegradability, which render them ideal candidates for wound healing applications. Combining them with inorganic and organic moieties can produce effective multifunctional composites with the desired mechanical properties, high wound healing efficiencies and excellent antibacterial behavior. Recent research endeavors focus on the development of stimuli-responsive polysaccharide composites for biomedical applications. Polysaccharide composites, being sensitive to the local environment, such as changes of the solution temperature, pH, etc., can sense and react to the wound conditions, thus promoting an effective interaction with the wound. This review highlights the recent advances in stimuli-responsive polysaccharide hydrogels and their composites for use in wound healing applications. The synthetic approaches, physical, chemical, and biochemical properties as well as their function in wound healing will be discussed.