Macromolecular bioscience最新文献

Chronic wounds (CWs) are characterized by persistent inflammation and bacterial biofilms, which hinder healing and contribute to antibiotic resistance. Therefore, innovative treatments with both anti-inflammatory and antibiofilm properties are urgently needed. Here, cobalt phthalocyanine (CoPc), a photo-excitable dye, is combined with polyphenolic lignin to develop CoPc-Lig nanoparticles (NPs). These NPs demonstrate antioxidant activity by scavenging reactive oxygen species and inhibiting key enzymes implicated in CW pathophysiology. Moreover, they are internalized into Staphylococcus aureus and Pseudomonas aeruginosa biofilms, a critical feature for enhancing antibacterial effects. Upon near-infrared light excitation, CoPc-Lig NPs produce a thermal increase, which reduces bacterial viability and disrupts biofilm integrity. This mild photothermal effect is particularly advantageous in CW treatment, as excessive temperatures can damage newly formed tissue. Additionally, the NPs exhibit strong photoacoustic (PA) properties, enabling their use in PA imaging, an emerging non-invasive technique for real-time monitoring. The PA signal remains stable over time and is detected in ex vivo tissue phantoms. These findings highlight the potential of CoPc-Lig NPs as a theragnostic platform for CW management, integrating antimicrobial cobalt, antioxidant polyphenols, and photo-excitable phthalocyanines. Future studies will focus on optimizing photothermal treatment conditions and exploring synergies with debridement and antibacterial agents to enhance therapeutic outcomes.

Hydrogels prepared from gelatin are ideal for mimicking the extracellular matrix (ECM) owing to their inherent cell-adhesive and protease-labile peptide sequences. While gelatin is highly water-soluble, it does not form the triple-helical structure. As a result, physically crosslinked gelatin-based hydrogels are only stable at low temperatures, precluding their use in 3D cell culture. Gelatin-methacryloyl (GelMA) and gelatin-norbornene (GelNB) have been developed to enable the stable crosslinking of gelatin-based hydrogels via chain-growth or step-growth photopolymerization. However, most gelatin-based hydrogels lack dynamically tunable properties unless macromers with dynamically crosslinkable motifs are used. Here, we integrate GelNB with dithiolane-containing crosslinker poly(ethylene glycol)-tetra-lipoic acid (PEG4LA)-for modular photo-crosslinking of GelNB into hydrogels under cytocompatible light exposure (365 nm, 5 mW/cm²) with a low photoinitiator concentration (1 mm LAP). Even under these mild reaction conditions, the stiffness of GelNB/PEG4LA hydrogels could be dynamically tuned by inducing dithiolane ring-opening via secondary light exposure, thereby creating dynamic and cytocompatible hydrogels suitable for in situ encapsulation, culture, and differentiation of human induced pluripotent stem cells (hiPSCs).

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.

Infection sites and open wounds provide a prime environment for the growth of opportunistic pathogens, leading to persistent infections caused by bacteria that contain antimicrobial-resistant phenotypes. Mistreatment of these wound infections often increases antimicrobial resistance (AMR), thereby decreasing the effectiveness of antibiotics. With the increase in AMR, new antimicrobial therapeutics that target these hard-to-kill pathogens are needed. Herein, naturally harvested bacteriophages (ECΦ) were combined with another established antimicrobial molecule, nitric oxide (NO). This combination has rarely been explored in biomedical devices but shows excellent potential for developing broad-spectrum, antibacterial materials. Bacteriophages were encapsulated in alginate microbeads and suspended in a NO-releasing thermoresponsive hydrogel. The phages were shown to have a delayed release from the alginate beads when incorporated into the gel, compared to the release observed within 24 h in aqueous medium. This delayed release enabled tunable phage delivery by adjusting the viscosity of the bulk gel base. Additionally, we used alginate as the base for microbeads, resulting in a physiologically safe material due to its proven biocompatibility. The final ECΦ and NO-releasing bead-gel matrix demonstrated 5-10 times larger zones of bacterial killing while maintaining low cytotoxicity, enabling further development in various clinical applications, including wound healing.

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.