Macromolecular bioscience最新文献

3D cancer models can mimic the tumor microenvironment, serving as a physiologically relevant platform to investigate the behavior of tumors and test anticancer therapeutics. Although bioactive peptide hydrogels have been widely evaluated for tissue engineering applications, their potential in 3D cancer models has been confirmed in only a few studies. In this study, self-assembling peptide hydrogels containing LDV (IBP1) and LDV and IKVAV cell attachment motifs (IBP2), and the control hydrogel without adhesion units (KLEI) were used for lung cancer modeling. The peptides self-assembled into hydrogels in a cell culture medium with storage moduli of ∼700–1500 Pa. The IBP1 and IBP2 hydrogels enhanced A549 cell proliferation and induced the formation of spheroids with average diameters between ∼70 and ∼150 µm. The cells in KLEI hydrogel with the highest stiffness exhibited mesenchymal-type migration, independent of the cell population, whereas transformation to mesenchymal migration necessitated a specific cell population in the IBP2 hydrogel. The cells in the IBP1 and IBP2 hydrogels with enhanced cell-cell interactions demonstrated higher resistance to docetaxel (DTX). Thus, our results indicate that these bioactive hydrogels can serve as a promising platform for in vitro assessment of cancer mechanisms and drug screening.

Excessive fibrosis impairs tissue regeneration by promoting extracellular matrix deposition and fibroblast activation. This study introduces keratin-based hydrogels (KRT) derived from residual human hair as sustainable carriers for localized atorvastatin (Ator) delivery. Calcium incorporation (CKRT) enhanced electrostatic interactions with Ator, improving sequestration and modulating release kinetics. Comprehensive characterization of KRT included chemical composition (FTIR, DSC), charge properties (pI = 5.5; net negative charge = −15.43 µmol/g), porosity (89%), and rheology (shear-thinning, linear viscoelastic region up to 24.5% strain, thermal stability to 68°C). Ator release followed Korsmeyer-Peppas kinetics (r² > 95%), and finite element analysis validated experimental profiles (r² = 82%–95%) while estimating diffusivity reductions from 569 to 0.06 µm²/s within the gel matrix. In vitro assays confirmed CKRT biocompatibility (ISO 10993–5) and preserved Ator bioactivity, with EC₅₀ values of 208 µm for mesenchymal stem and 389 µm for fibroblast cell lines. These findings demonstrate that CKRT provides a robust platform for controlled anti-fibrotic drug delivery, supported by extensive physicochemical and mechanical characterization.

Wound healing is a complex and dynamic biological process involving multiple phases, including inflammation, proliferation, and tissue remodeling. Despite significant advances in therapeutic approaches, conventional wound healing treatments often suffer from limitations such as poor bioavailability of drugs, inadequate moisture retention, uncontrolled release profiles, and delayed tissue regeneration. To overcome these challenges, drug-loaded nanocrystals were incorporated into an alginate-based hydrogel matrix to develop a biocompatible and sustained-release wound dressing. Emodin, a natural anthraquinone compound with potent anti-inflammatory, antioxidant, and antimicrobial properties, was used as the therapeutic agent. The combination of emodin nanocrystals with the alginate hydrogel resulted in a synergistic effect, providing enhanced drug stability, controlled release, and accelerated tissue regeneration. The developed NCs-hydrogel composite demonstrates significant potential as an advanced wound dressing material, offering an effective and biocompatible platform for promoting rapid wound healing.

Triple-negative breast cancer (TNBC) remains one of the most challenging breast cancer subtypes to treat due to the lack of well-defined molecular targets. Cluster of differentiation 13 (CD13), a cell surface aminopeptidase, is highly expressed in various tumors and play critical roles in promoting angiogenesis, aberrant proliferation, invasion, and metastasis. In this study, we investigated CD13 as a potential therapeutic target in TNBC cell lines to enable targeted therapy. Accordingly, we employed a protein cage nanoparticle, AaLS/TRAIL/aCD13Nb, which simultaneously displays CD13-binding nanobodies (aCD13Nb) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) via the SpyCatcher/SpyTag protein ligation system. This dual-ligand nanoparticle exhibited enhanced and specific binding to CD13-overexpressing TNBC cell lines, including HCC1937, MDA-MB-468, and BT-549 cells. aCD13Nb-mediated tight binding facilitated sustained interaction of TRAIL with death receptors, resulting in robust activation of apoptotic signaling cascades and significantly enhanced therapeutic efficacy in CD13-overexpressing TNBC cell lines. Moreover, systemic administration of AaLS/TRAIL/aCD13Nb via intravenous injection markedly suppressed tumor growth in an HCC1937 xenograft mouse model, without evidence of systemic toxicity. These findings validate CD13 as a promising therapeutic target in TNBC and underscore the potential of dual-ligand protein cage nanoparticles as an effective platform for targeted cancer therapy.

The skin is constantly exposed to external factors throughout a person's life, ultraviolet (UV) radiation being one of the most harmful. The primary defence against UV-induced damage is skin pigmentation, which is achieved through the synthesis of melanin. However, overproduction of melanin can lead to skin disorders such as pigment spots, melasma, and even melanoma. Therefore, the present study aimed to obtain a new multifunctional bioactive system (MBS) starting from a supramolecular co-assembled gel (SG) based on amino acids and short peptides enhanced with a glycoside-pyrone-based complex (arbutin-kojic acid), presenting an inhibitory effect on peroxidase and implicitly controlling melanin production. The MBS gel was physicochemically analyzed using FTIR to observe changes in its chemical structure after exposure to 4°C and 25°C. The results indicate that MBS remains stable for up to 12 weeks without chemical changes in structure when stored at 4°C. The potential applicability was evaluated by antioxidant activity, where the gel exhibited above 85% scavenging activity of DPPH· free radicals. The MBS displays synergistically strong ability to inhibit the catalytic activity, functioning as an uncompetitive inhibitor that binds specifically to the enzyme-substrate complex. The in vivo biosafety of the MBS was determined at 24 h and 7 days after rat administration. The hematological and biochemical parameters show that the MBS system is safe and biocompatible both after 24 h and after 7 days. The overall findings suggest that the MBS gel has promising potential as a regulator of melanogenesis by inhibiting skin melanin synthesis.

Neurodegenerative diseases represent a major global health challenge due to their progressive nature and lack of curative therapies. Developing innovative strategies to protect and regenerate neuronal structures is therefore crucial. In recent years, Sobetirome, a synthetic thyromimetic compound, has emerged as a promising therapeutic candidate for neurodegenerative disorders owing to its neuroprotective and regenerative potential. However, its clinical efficacy is limited by the poor permeability of the blood–brain barrier. Enhancing brain delivery through controlled transport systems could therefore improve therapeutic outcomes. In this study, Sobetirome was encapsulated into chitosan-based nanoparticles to enhance its stability, bioavailability, and blood–brain barrier penetration. An in vitro neurodegeneration model was established using SH-SY5Y cells treated with lysophosphatidylcholine, and a Caco-2 cell line was used to evaluate blood–brain barrier permeability. The nanoparticles showed an average size of 137.7 nm, a low polydispersity index (0.1), and a zeta potential of +21 mV, indicating stability and uniformity. FTIR analysis confirmed successful drug encapsulation, while encapsulation and loading efficiencies reached 91.2% and 65.15%, respectively. In vitro release studies demonstrated a controlled release profile, with 73.39% of Sobetirome released after 32 h. Cellular assays revealed that Sobetirome-loaded nanoparticles enhanced SH-SY5Y cell viability, proliferation, neuroprotection, and regenerative effects compared to free Sobetirome. Lower nanoparticle concentrations reduced apoptosis and improved cellular uptake. SEM imaging confirmed spherical morphology and nanoscale dimensions, consistent with DLS measurements. Overall, these results suggest that Sobetirome-loaded chitosan nanoparticles are a promising platform for neurodegenerative disease therapy, providing improved bioavailability, controlled drug release, and potential for systemic delivery to optimize therapeutic outcomes.