Peptide-Based Nanoparticles Suppress Hepatic Inflammation via Blockage of Human Antigen R.

Human antigen R (HuR), which is a mRNA-binding protein that stabilizes and regulates mRNA translation, is found to have increased expression in inflammation, cancer and other diseases, making HuR to be a promising drug target. This study reports a peptide-based nanoparticle (NP) system exhibits potent anti-inflammatory activity to ameliorate acute liver injury via the ability of peptides to inhibit the mRNA binding site of HuR and block downstream signaling. Molecular modeling provided structural evidence indicating that the peptides interact with the RNA-binding site of HuR, mainly via hydrogen-bonding and hydrophobic interactions.

Antibacterial Gelatin Composite Hydrogels Comprised of In Situ Formed Zinc Oxide Nanoparticles.

We report the feasibility of using gelatin hydrogel networks as the host for the in situ, environmentally friendly formation of well-dispersed zinc oxide nanoparticles (ZnONPs) and the evaluation of the antibacterial activity of the as-prepared composite hydrogels. The resulting composite hydrogels displayed remarkable biocompatibility and antibacterial activity as compared to those in previous studies, primarily attributed to the uniform distribution of the ZnONPs with sizes smaller than 15 nm within the hydrogel network. In addition, the composite hydrogels exhibited better thermal stability and mechanical properties as well as lower swelling ratios compared to the unloaded counterpart, which could be attributed to the non-covalent interactions between the in situ formed ZnONPs and polypeptide chains.

The Use of Sensors in Blood-Brain Barrier-on-a-Chip Devices: Current Practice and Future Directions.

The application of lab-on-a-chip technologies in in vitro cell culturing swiftly resulted in improved models of human organs compared to static culture insert-based ones. These chip devices provide controlled cell culture environments to mimic physiological functions and properties. Models of the blood-brain barrier (BBB) especially profited from this advanced technological approach.

Targeting Human Endothelial Cells with Glutathione and Alanine Increases the Crossing of a Polypeptide Nanocarrier through a Blood-Brain Barrier Model and Entry to Human Brain Organoids.

Nanoparticles (NPs) are the focus of research efforts that aim to develop successful drug delivery systems for the brain. Polypeptide nanocarriers are versatile platforms and combine high functionality with good biocompatibility and biodegradability. The key to the efficient brain delivery of NPs is the specific targeting of cerebral endothelial cells that form the blood-brain barrier (BBB).

Polypeptide Bilayer Assembly-Mediated Gene Delivery Enhances Chemotherapy in Cancer Cells.

Developing gene vectors with high transfection efficiency and low cytotoxicity to humans is crucial to improve gene therapy outcomes. This study set out to investigate the use of cationic polypeptide bilayer assemblies formed by coil-sheet poly(l-lysine)--poly(l-benzyl-cysteine) (PLL--PBLC) as gene vectors that present improved transfection efficiency, endosomal escape, and biocompatibility compared to PLL. The formation of the polyplexes was triggered by hydrogen bonding, hydrophobic interactions, and electrostatic association between the cationic PLL segments and the negatively charged plasmid encoding p53, resulting in self-assembled polypeptide chains.

Cellular Therapy Using Epitope-Imprinted Composite Nanoparticles to Remove α-Synuclein from an In Vitro Model.

Several degenerative disorders of the central nervous system, including Parkinson's disease (PD), are related to the pathological aggregation of proteins. Antibodies against toxic disease proteins, such as α-synuclein (SNCA), are therefore being developed as possible therapeutics. In this work, one peptide (YVGSKTKEGVVHGVA) from SNCA was used as the epitope to construct magnetic molecularly imprinted composite nanoparticles (MMIPs).

Synthesis and Hydrogelation of Star-Shaped Graft Copolypetides with Asymmetric Topology.

To study the self-assembly and hydrogel formation of the star-shaped graft copolypeptides with asymmetric topology, star-shaped poly(-lysine) with various arm numbers were synthesized by using asymmetric polyglycerol dendrimers (PGDs) as the initiators and 1,1,3,3-tetramethylguanidine (TMG) as an activator for OH groups, followed by deprotection and grafting with indole or phenyl group on the side chain. The packing of the grafting moiety via non-covalent interactions not only facilitated the polypeptide segments to adopt more ordered conformations but also triggered the spontaneous hydrogelation. The hydrogelation ability was found to be correlated with polypeptide composition and topology.

Incorporation of Glutamic Acid or Amino-Protected Glutamic Acid into Poly(Glycerol Sebacate): Synthesis and Characterization.

Poly(glycerol sebacate) (PGS), a soft, tough elastomer with excellent biocompatibility, has been exploited successfully in many tissue engineering applications. Although tunable to some extent, the rapid in vivo degradation kinetics of PGS is not compatible with the healing rate of some tissues. The incorporation of L-glutamic acid into a PGS network with an aim to retard the degradation rate of PGS through the formation of peptide bonds was conducted in this study.

A Triple Combination of Targeting Ligands Increases the Penetration of Nanoparticles across a Blood-Brain Barrier Culture Model.

Nanosized drug delivery systems targeting transporters of the blood-brain barrier (BBB) are promising carriers to enhance the penetration of therapeutics into the brain. The expression of solute carriers (SLC) is high and shows a specific pattern at the BBB. Here we show that targeting ligands ascorbic acid, leucine and glutathione on nanoparticles elevated the uptake of albumin cargo in cultured primary rat brain endothelial cells.

ZnO-loaded DNA nanogels as neutrophil extracellular trap-like structures in the treatment of mouse peritonitis.

Neutrophil extracellular traps (NETs) are chromatin-based structures that are released from neutrophils during infections and prevent microbes from spreading in the body through efficient degradation of their composition. Based on this chromatin-driven strategy of capturing and killing bacteria, we designed NET-like structures using DNA and ZnO nanoparticles (NPs). DNA was first purified from kiwifruit and treated with HCl to increase hydroxyl groups in the opened-deoxylribose form.

Advances in the Application of Nanomaterials as Treatments for Bacterial Infectious Diseases.

Bacteria-targeting nanomaterials have been widely used in the diagnosis and treatment of bacterial infectious diseases. These nanomaterials show great potential as antimicrobial agents due to their broad-spectrum antibacterial capacity and relatively low toxicity. Recently, nanomaterials have improved the accurate detection of pathogens, provided therapeutic strategies against nosocomial infections and facilitated the delivery of antigenic protein vaccines that induce humoral and cellular immunity.

Polypeptide Composition and Topology Affect Hydrogelation of Star-Shaped Poly(-lysine)-Based Amphiphilic Copolypeptides.

In this research, we studied the effect of polypeptide composition and topology on the hydrogelation of star-shaped block copolypeptides based on hydrophilic, coil poly(-lysine) (-PLL) tethered with a hydrophobic, sheet-like polypeptide segment, which is poly(-phenylalanine) (PPhe), poly(-leucine) (PLeu), poly(-valine) (PVal) or poly(-alanine) (PAla) with a degree of polymerization (DP) about 5. We found that the PPhe, PLeu, and PVal segments are good hydrogelators to promote hydrogelation. The hydrogelation and hydrogel mechanical properties depend on the arm number and hydrophobic polypeptide segment, which are dictated by the amphiphilic balance between polypeptide blocks and the hydrophobic interactions/hydrogen bonding exerted by the hydrophobic polypeptide segment.

Naturally derived DNA nanogels as pH- and glutathione-triggered anticancer drug carriers.

Conventional chemotherapeutic drugs are nonselective and harmful toward normal tissues, causing severe side effects. Therefore, the development of chemotherapeutics that can target cancer cells and improve therapeutic efficacy is of high priority. Biomolecules isolated from nature serve as green solutions for biomedical use, solving biocompatibility and cytotoxicity issues in human bodies.

Biomimetic hydrogels based on L-Dopa conjugated gelatin as pH-responsive drug carriers and antimicrobial agents.

Biomimetic hydrogels which possess good biocompatibility, high degradability, and low toxicity as well as good antibacterial activity against various bacteria would potentially be promising for biomaterial applications, such as wound healing, tissue engineering, and payload delivery systems. Herein, we report the synthesis and hydrogelation of L-Dopa conjugated (GPLD) polypeptides via a versatile strategy including enzymatic cross-linking or coordinated/oxidized cross-linking with Fe ions and demonstrated the feasibility of loading cancer drug and metal NPs in hydrogel matrix. The drug-loaded hydrogel was simply prepared via coordinated/oxidized cross-linking by Fe and HO within short gelation time.

Peptide Fibrillar Assemblies Exhibit Membranolytic Effects and Antimetastatic Activity on Lung Cancer Cells.

Cancer metastasis is a central oncology concern that worsens patient conditions and increases mortality in a short period of time. During metastatic events, mitochondria undergo specific physiological alterations that have emerged as notable therapeutic targets to counter cancer progression. In this study, we use drug-free, cationic peptide fibrillar assemblies (PFAs) formed by poly(L-Lysine)--poly(L-Threonine) (Lys--Thr) to target mitochondria.

Catalase immobilized in polypeptide/silica nanocomposites via emulsion and biomineralization with improved activities.

Polypeptide-mediated silica mineralization is an attractive approach to prepare polypeptide/silica nanocomposites for enzyme immobilization. Herein, a facile approach for in situ immobilization of catalase (CAT) in polypeptide/silica nanocomposites is developed via the preparation of cross-linked polypeptide/enzyme microgels using an emulsion process followed by silica mineralization. The efficient protein immobilization under benign condition (25-28 °C, pH 7.

Antibacterial polypeptide/heparin composite hydrogels carrying growth factor for wound healing.

We report an efficient growth factor delivering system based on polypeptide/heparin composite hydrogels for wound healing application. Linear and star-shaped poly(l-lysine) (l-PLL and s-PLL) were chosen due to not only their cationic characteristics, facilitating the efficient complexation of negatively charged heparin, but also the ease to tune the physical and mechanical properties of as-prepared hydrogels simply by varying polypeptide topology and chain length. The results showed that polymer topology can be an additional parameter to tune hydrogel properties.

In situ formation of silver nanoparticles-contained gelatin-PEG-dopamine hydrogels via enzymatic cross-linking reaction for improved antibacterial activities.

Hydrogels containing silver nanoparticles (AgNPs) were recently found to exhibit excellent antibacterial properties against both gram-negative/positive bacteria and fungi. In this study, we reported the synthesis of AgNPs-contained gelatin-polyethylene glycol-dopamine (AgNP-GPD) hydrogels via the in situ formation of AgNPs in GPD polypeptide solution, followed by an enzymatic cross-linking reaction to form hydrogels. The experimental results showed that the reducing reaction exerted by GPD polypeptides under physiological conditions can afford the formation of AgNPs in situ in the polypeptide solution without the need for additional reducing agents and/or processes such as UV or thermal treatments and then the hydrogelation of GPD polypeptide solution containing AgNPs were preceeded via enzymatic cross-linking reaction.

Green synthesis of gold nanoparticle/gelatin/protein nanogels with enhanced bioluminescence/biofluorescence.

Here we report the green synthesis of gelatin/protein hybrid nanogels containing gold nanoparticles (AuNPs) that collectively exhibit metal-enhanced luminescence/fluorescence (MEL/MEF). The gelatin/protein nanogels, prepared by genipin cross-linking of preformed gelatin/protein polyion complexes (PICs), exhibited sizes ranging between 50 and 200 nm, depending on the weight ratio of gelatin and protein. These nanogels serve as reducing and stabilizing agents for the AuNPs, allowing for nucleation in a gel network that exhibits colloidal stability and MEL/MEF.

Star-shaped polypeptides exhibit potent antibacterial activities.

Peptide-based biomaterials are a promising class of antimicrobial agents that work by physically damaging bacterial cell membranes rather than targeting intracellular factors, resulting in less susceptibility to drug resistance. Herein we report the synthesis of cationic, star-shaped polypeptides with 3 to 8 arms and their evaluation as antimicrobial agents against different types of bacteria. The effects of the arm number and side chain group on their antimicrobial activities were systematically investigated.

TRAIL encapsulated to polypeptide-crosslinked nanogel exhibits increased anti-inflammatory activities in Klebsiella pneumoniae-induced sepsis treatment.

Bacterial infections are often treated inadequately. Sepsis, being one of its most severe forms, is a multi-layered, life-threatening syndrome induced by rampant immune responses, like cytokine storms, that leads to high morbidity and death of infected patients. Particularly, the current increment in resistant bacterial strains and the lack of creative antibiotics to counter such menace are central reasons to the worsening of the situation.

Synthesis of silica/polypeptide hybrid nanomaterials and mesoporous silica by molecular replication of sheet-like polypeptide complexes through biomimetic mineralization.

Biomimetic synthesis of silica/polymer hybrid nanomaterials inspired by silica-condensing microorganisms has gained significant advances in recent years and the as-prepared hybrid materials have been explored for a variety of applications. In this work, silica/polypeptide hybrid nanoparticles (NPs) and coating films can be facilely fabricated by silica mineralization of poly(l-lysine)-block-poly(l-threonine)/poly(l-glutamic acid) (PLL-b-PLT/PGA) fibril complexes assembled in solutions or on substrates at benign conditions. The experimental data revealed that PLL-b-PLT can self-assemble to form fibrils via intermolecular hydrogen bonding interactions between PLT chains and, upon complexing with PGA, silicas were efficiently mineralized in both the sheet-like PLL/PGA complexes and PLT domains, resulting in the fabrication of silica/polypeptide hybrid materials.