Biomacromolecules最新文献

Neuropeptide Y receptor Y1 (NPY1R) is an excellent potential target in glioma. This study aims to prepare ⁶⁸Ga/²¹¹At-labeled NPY1R-targeting peptide as radiopharmaceuticals for glioma-targeted imaging and therapy. Molecular operating environment (MOE) was used for mutation scanning and design peptide sequences. The peptide KINWKFRLRY (KINW) showed low cytotoxicity and efficient tumor targeting. ⁶⁸Ga-labeled KINW demonstrated the enhanced uptake in U87-MG cell xenograft models, confirming the potential imaging for glioma. KINW-conjugated N-succinimidyl-3-(trimethylstannyl) benzoate (m-MeATE) with ²¹¹At labeling (²¹¹At-ATE-KINW) exhibited a better stability and higher cellular than free ²¹¹At. ²¹¹At-ATE-KINW suppressed Akt/GSK3β/β-catenin signaling, reducing invasion, migration, and proliferation in U87-MG cells. Biodistribution revealed minimal normal tissue retention of ²¹¹At-ATE-KINW. Moreover, ²¹¹At-ATE-KINW had better tumor growth inhibition and significantly prolonged survival in U87-MG cell xenograft models compared to free ²¹¹At. Thus, a novel specific NPY1R peptide has potential to be applied in development of ⁶⁸Ga/ ²¹¹At-labeled radiopharmaceuticals for glioma-targeted imaging and therapy.

Conventional tumor starvation via embolization or glucose oxidase (GOx) is often hampered by poor specificity and enzyme instability. Herein, we developed a pH-responsive, amphiphilic GOx-conjugated polymer (LPHF-GOx) for synergistic cascade starvation therapy. Triggered by the acidic tumor microenvironment, LPHF-GOx undergoes rapid aggregation, achieving dual metabolic disruption through localized vascular embolization and GOx-mediated glucose depletion. LPHF-GOx demonstrated robust pH-dependent self-assembly while maintaining high catalytic activity. In vitro and in vivo evaluations confirmed that this dual-action system induces profound nutrient deprivation and oxidative stress, leading to significant tumor growth inhibition with negligible systemic toxicity. By integrating vessel occlusion with biochemical enzymatic interference, this study provides a potent and targeted platform for sustainable starvation therapy against malignant tumors.

Biofilm-associated infections present a critical healthcare challenge due to antibiotic resistance and frequent medical implant colonization. Preemptive surface coatings with antibiofilm properties are thus critical, yet conventional antifouling coatings only delay initial bacterial adhesion and poorly inhibit long-term biofilm formation. This study develops a versatile all-natural coating, combining phase-transited bovine serum albumin (PTB) as a structural matrix and a natural quorum-sensing inhibitor quercetin (Qe). The PTB framework delivers three core functions: stable adhesion to diverse substrates, immediate antifouling effects via reduced nonspecific protein/bacterial attachment, and sustained Qe release. Released Qe disrupts bacterial communication to inhibit biofilm maturation without bactericidal effects. Targeting both initial adhesion and maturation, this dual-action coating achieves broad-spectrum, prolonged antibiofilm activity against clinically significant pathogens, including Pseudomonas aeruginosa and Staphylococcus aureus. Its all-natural components ensure excellent cytocompatibility, rendering this facilely fabricated coating a safe, promising solution for biomedical antibiofilm applications.

Polydepsipeptides (PDPs) are biocompatible polymers, whose biodegradation releases only amino acids and glycolic or lactic acids, nontoxic compounds that are naturally present in the body. These polymers therefore have great potential as materials for use in biomedical applications, particularly as drug delivery systems. Here, we investigated the organocatalyzed ring-opening polymerization (OROP) of 3-benzylmorpholine-2,5-dione (MD(Phe)) using DBU and TU as the catalytic couple to synthesize PDP(Phe) with molar masses from 2.5 to 10 kg·mol^-1. Copolymerization with lactide was also studied, with the aim of obtaining various degradation kinetics related to the enzymatic environment. PDP(Phe)- and P(MD-co-LA)-based microparticles were produced by microfluidics with diameters of 40-60 μm and narrow size distributions. Their degradation behavior was evaluated in PBS and in the presence of enzymes (esterase, α-chymotrypsin). Both PDP(Phe) and P(MD-co-LA) microparticles displayed composition- and environment-dependent degradation, releasing phenylalanine and hydrolyzed MD(Phe).

Regenerated silk fibroin (RSF), obtained from the silk fibers of the species Bombyx mori, is a promising biomaterial due to its excellent mechanical and biological properties, as well as presenting versatility for applications in tissue engineering. This is particularly evident through the development of scaffolds via the 3D printing process. The viscosity of RSF solutions can be controlled by adding other synthetic polymers, thereby ensuring improved mechanical and rheological properties and enhanced quality of printed structures. The objective of this study is to investigate the rheological properties of gels based on RSF and PLDLA (poly(l-co-d,l-lactic acid)). The study involved the synthesis of PLDLA and the extraction of RSF from the silk threads of B. mori. Subsequently, RSF-PLDLA solutions in formic acid were prepared with varying concentrations, and subsequently subjected to rheological tests under steady-state and oscillatory regimes.

The clinical application of peptide therapeutics is often constrained by their short plasma half-life, necessitating frequent administration and resulting in undesirable pharmacokinetic fluctuations and side effects. Here, we developed a genetically encodable multivalent fusion protein platform that combines haemadin, a selective thrombin inhibitor derived from terrestrial leeches, with an elastin-like polypeptide (ELP) partner via factor Xa (FXa)-cleavable peptide linkers. This platform enables tunable drug loading, long-term release, and stimuli-responsive activation of antithrombotic activity. After subcutaneous injection, the fusion protein undergoes temperature-triggered ELP condensation to form an in situ depot that slowly releases an inactivated prodrug, which remains inert in circulation until thrombus-associated FXa cleave the linker to liberate active haemadin on demand. We achieved high-yield expression and facile nonchromatographic purification of the fusion protein. Subcutaneous administration resulted in significant prolongation of antithrombotic protection postinjection. This approach holds strong potential to enhance the safety, efficacy, and dosing convenience of peptide therapy.

Linear-dendritic block copolymers comprising poly(ε-caprolactone) attached to hydrophilic 2,2-bis(hydroxymethyl)propionic acid (bis-MPA) ester dendron via a disulfide and containing a defined number of pendent visible-light-responsive donor-acceptor Stenhouse adduct (DASA) groups are synthesized using click chemistry and postpolymerization modification. Self-assembly in aqueous solution selectively affords rice grain-like ellipsoidal, rod-like, and spherical micelles, governed by the number of DASA groups. Progressive disassembly of the micelles is observed during photoswitching cycles. Release of camptothecin depends on the DASA content under light irradiation and is enhanced by the synergistic effect of two stimuli. Cellular uptake quantified by FACS analysis is demonstrated to be influenced by the shape of the micelles, with ellipsoidal micelles exhibiting higher efficiency than spherical micelles by following clathrin- and caveolae-mediated endocytosis as major pathways for internalization. Both types of micelles were found to maintain the particle size in Dulbecco's modified Eagle's medium containing 10% fetal bovine serum at 37 ̊C. Doxorubicin (DOX)-loaded ellipsoidal micelles under photoirradiation show significantly higher apoptosis than free DOX.

Targeted therapy enables the selective delivery of therapeutics to specific cells, reducing off-target effects and improving efficacy. HER2-targeted approaches are particularly effective in HER2-positive breast cancer. Here, we engineered protein nanoparticles based on Aquifex aeolicus lumazine synthase (AaLS) to simultaneously display HER2-binding nanobodies (aHER2Nb; A10 or 2Rb17C) and/or TRAIL on their surface. Both single- and dual-ligand AaLS protein nanoparticles retained an intact cage architecture and showed strong binding to HER2-overexpressing breast cancer cells. Although SK-BR3 and MDA-MB-453 cells were resistant to soluble TRAIL, TRAIL-presenting AaLS (AaLS/TRAIL) markedly enhanced cytotoxicity by promoting death receptor clustering. Unexpectedly, dual-ligand AaLS protein nanoparticles (AaLS/TRAIL/A10 and AaLS/TRAIL/2Rb17C) exhibited biphasic cytotoxicity; low doses synergistically enhanced apoptosis in HER2-positive cells, whereas higher doses reduced efficacy, likely due to the activation of survival signaling. These results highlight the importance of dose optimization for maximizing the use of TRAIL-based targeted therapies.

Synthetic and natural materials with favorable structural support and biocompatibility are widely employed for tissue repair. To enhance their biological performance, surface modification with bioactive factors is commonly applied. However, most current methods lack modularity and versatility, limiting their broader application in regenerative medicine. In this work, we developed a bioactive material, termed SpyME, by integrating the mussel adhesive protein (MAP) and epidermal growth factor (EGF) with the Spycatcher-Spytag system. This construct exhibits strong and versatile adhesion to a variety of substrates via the MAP module, while maintaining the bioactivity of EGF. The combined use of SpyME and Hydrosorb hydrogel significantly accelerated full-thickness wound healing in a rat model compared to Hydrosorb alone. These results indicate that SpyME can effectively functionalize biomaterials, conferring enhanced bioactivity and improved therapeutic outcomes in biomedical applications. Furthermore, the modular design of SpyME offers broad potential for diverse applications, including growth factor immobilization and surface engineering of clinical implantable materials.

Self-supporting bilayer films were produced by combining a protein (casein or gelatin) and a polysaccharide (carboxymethylcellulose, CMC). Effective interfacial interactions, achieved either physically (primarily via electrostatic interactions) or chemically (with citric acid and 1,2,3,4-butanetetracarboxylic acid (BTCA) as cross-linkers), granted improved mechanical and functional performance. Gelatin layers exhibited strong adhesion across different pH values (3, 4.5, and 8), indicating a minimal role of electrostatic forces in interlayer interactions. In contrast, casein required the incorporation of tannic acid (TA) into the CMC layer as a compatibilizing agent to achieve effective adhesion. Polysaccharide cross-linkers were evaluated in casein-CMC bilayers, where citric acid reduced the water absorption, while BTCA improved water vapor barrier properties but decreased mechanical resistance. Understanding interfacial interactions enables the design of biobased materials with tailored properties, boosting competitiveness and functionality within the circular bioeconomy.