Macromolecular bioscience最新文献

Efficient intracellular protein delivery is of great importance for the development of protein-based therapy and modern biotechnologies. However, the hydrophilic and macromolecular nature of proteins greatly hinders their ability to cross cell membranes. Herein, a calixarene modification strategy for the intracellular delivery of protein drugs is developed. The decoration of sulfonate azocalix[4]arene (SAC4A) on proteins results in a nano-multivalent effect between Protein-S and amino acids on the cell surface, leading to efficient intracellular delivery of the protein via the clathrin-mediated endocytic pathway. By using SAC4A as a novel ligand, this calixarene modification strategy efficiently delivers 7 proteins, bovine serum albumin (BSA), trypsin (TRY), horseradish peroxidase (HRP), α-chymotrypsin (α-Chyt), lysozyme (LYZ), cytochrome C (Cyt C) and ribonuclease A (RNase A), into cells and significantly enhances the cytotoxicity of Cyt C and RNase A. Moreover, SAC4A-modified Cyt C demonstrates markedly enhanced antitumor efficacy in 4T1-bearing mice without notable side effects. Considering that these proteins are varied in molecular weight and isoelectric point, this calixarene modification strategy provides a platform technology for intracellular protein delivery and the development of protein drugs targeting intracellular pathways.

This article explores the hierarchical self-assembly of short peptides, which refers to the structured spatial arrangements of these molecules over long distances. This phenomenon is commonly found in nature and has important implications for biological structure and function. Short peptides are preferred for self-assembly because they have the ability to spontaneously create various nanostructures. This process, known as bottom-up assembly, allows for the addition of functional groups at the carboxyl or amine ends of the peptides. These functional groups enable specific functions that are extremely valuable in the fields of biotechnology and biomedicine. This text discusses the basic processes involved in the self-assembly of short peptides, such as the characteristics of amino acid side chains, the categorization of short peptides according to their chemical structure, the influence of intermolecular forces, and the dynamic nature of the self-assembly process. In addition, the paper discusses the various uses of short peptides in the disciplines of biomedicine and optoelectronics, including stimulus-responsive hydrogels, tissue engineering, and drug delivery. The article also suggests rational design principles for controlling the hierarchical self-assembly of short peptides, creating new commercial applications, particularly with functional hydrogels, and offers insights into the future of the discipline.

Chemotherapy is generally given by intravenous (IV) administration which provides higher bioavailability than other systemic routes. However, in the case of lung cancer, the pulmonary (INH) route is the other choice for inhalable formulations. In the study, biochemical and histological parameters of Cabazitaxel (CBZ) free (2 mg kg^-1) and nanoparticle (NP) (2 mg kg^-1 CBZ equivalent) formulations are investigated after IV and INH administration in rats. The nanoformulation of CBZ is obtained using PEGylated polystyrene (PEG-PST) nanoparticles obtained by PISA. While a nose and head-only device is used for INH administration, a jugular vein is used as the IV route. Blood samples (blank, 24 h, and 48 h) are collected via carotid artery cannulas without handling in metabolism cages. According to biochemical parameters, free CBZ formulation applied via IV or INH route shows higher systemic toxicity. On the other hand, the nanoformulation of CBZ showed no signs of toxicity in both IV or INH routes. Higher and longer retention is observed in the case of inhaled nanoformulation. Histological analysis showed higher alveolar macrophage migration for inhaled nanoformulation due to enhanced retention. Results showed that nanotechnology and the lung defense system gave the advantage to end up with an inhalable nanomedicine formulation for lung cancer.

Adhesive hydrogels are emerging as attractive functional materials for various fields, such as tissue engineering, wound healing, E-skins, etc. However, the removal of adhesive hydrogels from covered area may be painful and cause a secondary damage. In the current study, gelatin-based hydrogels are prepared by cross-linking with tannic acid and 4-formylphenyl boronic acid, through simultaneous dynamic covalent boronic ester and imine bond formations. The obtained hydrogels not only present self-healing and injectable properties, but also show tunable adhesiveness that regulated by temperature and oxidation degrees of tannic acid. The maximum adhesion strength of the hydrogels with medium oxidation degree at 37 °C can be measured up to 30 kPa on porcine skin, while the value decreased to ≈10 kPa at lowered temperature of 25 °C, facilitating the unpainful removal of the hydrogels from skins. This work provides a new approach for the design of functional hydrogels with tailorable adhesiveness.

There has been limited exploration of carbon nanofiber as a scaffold for cellular attachment and proliferation. In this work, commercially available, pyrolytically stripped carbon nanofiber (cCNF) is deposited over electrospun nanofiber mats, polycaprolactone (PCL) and poly(D-lactide) (PDLA), to immobilize them and investigate whether the 3D cCNF layer's surface augments cell proliferation of human dermal fibroblasts (nHDF). Spectral characterizations, such as XRD and Raman, show that cCNF exhibited crystalline structure with a high graphitization degree. cCNF layers are modified to have an irregular or planar surface by simple agitation (s-cCNF) or probe sonication (p-cCNF) of the solution. The in vitro cell line studies revealed that p-cCNF is better than s-cCNF in providing a platform that supports a homogenous spread of the fibroblasts all over the nanofiber's surface. The p-cCNF-deposited PCL mat (p-cCNF@PCL) demonstrated cellular growth, similar to that of the neat PCL mat. However, the p-cCNF@PCL mat exhibited remarkable antibacterial properties by reducing the E. coli numbers, ≈16 times greater than the PCL mat. It is concluded that the immobilized, pyrolytically stripped carbon nanofiber's surface has the potential to accommodate cellular growth and inhibit bacterial colonies, suggesting the biomaterial scaffold is promising for in vivo and clinical applications of skin tissue regeneration.

Glycosaminoglycans (GAGs) play a pivotal role in pathogen attachment and entry into host cells, where the interaction with GAGs is critical for a diverse range of bacteria and viruses. This study focuses on elucidating the specific interactions between sulfated GAGs and the adhesin OmcB (Outer membrane complex protein B) of Chlamydia species, examining how structural characteristics of GAGs, such as sulfation degree and molecular weight, influence their binding affinity and thereby affect bacterial infectivity. A surface-based binding assay is established to determine the binding constants of OmcB with various GAGs. It is shown that increased sulfation and higher molecular weight enhance GAG binding to OmcB. These findings are further validated using cell assays, which shows that the addition of sulfated GAGs reduces OmcB-cell binding and inhibits the attachment of C. pneumoniae elementary bodies (EBs), underscoring the pivotal role of specific GAGs in chlamydial infections. Notably, heparin exhibites a stronger inhibitory effect on OmcB compare to GAGs with similar sulfation degrees and molecular weights, suggesting that particular molecular architectures may optimize binding interactions.

The 3D printing of human tissue constructs requires carefully designed bioinks to support the growth and function of cells. Here it is shown that an additional parameter is how drug-releasing microparticles affect the material properties of the scaffold. A microfluidic platform is used to create all-trans retinoic acid (atRA) polycaprolactone (PCL) microparticles with a high encapsulation efficiency (85.9 ± 5.0%), and incorporate them into fibrin constructs to investigate their effect on the material properties. An encapsulation that is around 25-35% higher than the current state of the art batch methods is achieved. It is also found that the drug loading concentration affects the microparticle size, which can be controlled using the microfluidic platform. It is shown that the release of atRA is slower in fibrin constructs than in buffer, and that the presence of atRA in the microparticles modulates both the degradation and the rheological properties of the constructs. Finally, it is shown that the fibrin material exhibits a stronger solid-like state in the presence of atRA-PCL microparticles. These findings establish a basis for understanding the interplay between drug-releasing microparticles and scaffold materials, paving the way for bioinks that achieve tailored degradation and mechanical properties, together with sustained drug delivery for tissue engineering applications.

Regenerating skin tissue remains a major challenge in medical science, especially due to the risk of scarring and prolonged healing, which becomes even more complicated in people with diabetes. Recent advancements have led to the creation of therapeutic dressings incorporating drug-delivery systems to tackle these issues. Exosomes (Exos) derived from mesenchymal stem cells (MSCs) have gained significant attention for mediating therapy without directly using cells, thanks to their natural anti-inflammatory and tissue repair properties mirroring those of MSCs. In this study, an advanced wound dressing combines chitosan (CS) and polyethylene glycol (PEG) hydrogel with adipose MSCs-derived Exos (ADMSCs-Exos). This composite, formed using a straightforward blending technique, is engineered to improve the healing process of severe skin injuries by steadily releasing Exos as the hydrogel degrades. The in vitro studies demonstrate that this hydrogel-exosome dressing greatly enhances endothelial cell migration, reduces oxidative stress, and promotes angiogenesis, crucial for effective wound healing. Additionally, real time-polymerase chain reaction (RT-PCR) analysis revealed significant upregulation of key genes involved in these processes, supporting the therapeutic potential of the hydrogel-Exo combination. These findings emphasize the potential of this hydrogel-Exos combination as an innovative and promising solution for advanced wound care.

Polymeric nanoarchitectures are crafted from amphiphilic block copolymers through a meticulous self-assembly process. The composition of these block copolymers is finely adjustable, bestowing precise control over the characteristics and properties of the resultant polymeric assemblies. These nanoparticles have garnered significant attention, particularly in the realm of biological sciences, owing to their biocompatibility, favorable pharmacokinetics, and facile chemically modifiable nature. Among the myriad of polymeric nanoarchitectures, micelles and polymersomes stand out as frontrunners, exhibiting much potential as cargo carrier systems for diverse bio-applications. This review elucidates the design strategies employed for amphiphilic block copolymers and their resultant assemblies, specifically focusing on micelles and polymersomes. Subsequently, it discusses their wide-ranging bio-applications, spanning from drug delivery and diagnostics to bioimaging and artificial cell applications. Finally, a reflective analysis will be provided, highlighting the current landscape of polymeric cargo carriers, and discussing the opportunities and challenges that lie ahead. With this review, it is aimed to summarize the recent advances in polymeric assemblies and their applications in the biomedical field.

Soft tissue integration (STI) around dental implants determines their long-term success, and the key is to immediately construct a temporary soft tissue-like barrier to prevent bacterial invasion after implantation and then, promote STI. In response to this need, an injectable multi-crosslinked hydrogel (MCH) with abilities of self-healing, anti-swelling, degradability, and dry/wet adhesion to soft tissue/titanium is developed using gallic acid-graft-chitosan, oxidized sodium alginate, gelatin, and Cu²⁺ with water and borax solution as solvents, whose properties can be controlled by adjusting its composition and ratio. MCH can not only immediately build a sealing barrier to block the bacterial invasion in the oral simulation environment but also deliver outstanding antibacterial efficacy through the synergism of trapping bacteria and releasing bactericidal agents such as chitosan, gallic acid, aldehyde, and Cu²⁺. Moreover, MCH has an adjustable ROS-scavenging ability imparted by gallic acid, chitosan, and gelatin to reduce inflammation and can control the release of Cu²⁺. Based on these, it is believed that by injecting MCH around implants (percutaneous/transmucosal) after surgery, a universal non-aggressive strategy to promote STI can be developed for long-term implant success.