Simultaneous antioxidant and neuroprotective effects of two-dimensional (2D) MXene-loaded isoquercetin for ischemic stroke treatment.

Oxidative stress and reactive oxygen species drive ischemic stroke and its related complications. New antioxidant medications are therefore crucial for treating ischemic stroke. We developed TiC@BSA-ISO nanocomposites loaded with the hydrophobic drug isoquercetin (ISO) encapsulated in BSA on TiC nano-enzymes as a novel therapeutic nanomedicine for the treatment of ischemic stroke targeting reactive oxygen species (ROS).

Antioxidant-Engineered Milk-Derived Extracellular Vesicles for Accelerating Wound Healing via Regulation of the PI3K-AKT Signaling Pathway.

Inspired by the experience of relieving inflammation in infants with milk, antioxidant-engineered milk-derived extracellular vesicles (MEVs) are developed to evaluate their potential for accelerating wound healing. In this work, MEVs with polydopamines (PDA) are engineered using the co-extrusion method. Subsequently, the authors incorporated them into a Schiff-based crosslink hydrogel, forming a skin dosage form that could facilitate the wound healing process.

Native and engineered exosomes for inflammatory disease.

Exosomes are extracellular vesicles which carry specific molecular information from donor cells and act as an intercellular communication vehicle, which have emerged as a novel cell-free strategy for the treatment of many diseases including inflammatory disease. Recently, rising studies have developed exosome-based strategies for novel inflammation therapy due to their biocompatibility and bioactivity. Researchers not only use native exosomes as therapeutic agents for inflammation, but also strive to make up for the natural defects of exosomes through engineering methods to improve and update the property of exosomes for enhanced therapeutic effects.

HACE2-Exosome-Based Nano-Bait for Concurrent SARS-CoV-2 Trapping and Antioxidant Therapy.

Corona Virus Disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is seriously threatening human health. Following SARS-CoV-2 infection, immune cell infiltration creates an inflammatory and oxidative microenvironment, which can cause pneumonia, severe acute respiratory syndrome, kidney failure, and even death. Clinically, a safe and effective treatment strategy remains to be established.

Antibiotics armed neutrophils as a potential therapy for brain fungal infection caused by chemotherapy-induced neutropenia.

Chemotherapy-induced neutropenia, a symptom of neutrophil depletion, makes cancer patients highly susceptible to invasive fungal infection with substantial morbidity and mortality. To address the cryptococcal brain infection in this condition, this study attempts to arm neutrophils (NEs) with antibiotics to potentiate the antifungal capability of NEs. To allow effective integration, amphotericin B, a potent antibiotic, is assembled with albumin nanoparticles through hydrophobic and hydrogen-bond interactions to form AmB@BSA nanoparticles (A-NPs).

A vaccine for photodynamic immunogenic cell death: tumor cell caged by cellular disulfide-thiol exchange for immunotherapy.

It has been suggested that immunogenic cell death (ICD) has therapeutic potential; however, its anticancer immunity is considerably hampered by the in situ immunosuppressive microenvironment within the tumor area, such as the dysfunction of antigen-presenting cells. Herein, we present an in vitro ICD-inducing modality to circumvent such impairment of immune activation. To this end, a "hot", i.

Nanoparticle reinforced bacterial outer-membrane vesicles effectively prevent fatal infection of carbapenem-resistant Klebsiella pneumoniae.

Infection resulting from carbapenem-resistant Klebsiella pneumoniae (CRKP) is an intractable clinical problem. Outer membrane vesicles (OMVs) from CRKP are believed to be potential vaccine candidates. However, their immune response remains elusive due to low structural stability and poor size homogeneity.

Self-Albumin Camouflage of Carrier Protein Prevents Nontarget Antibody Production for Enhanced LDL-C Immunotherapy.

Elevated low-density lipoprotein cholesterol (LDL-C) increases the risk of atherosclerotic cardiovascular disease. Peptide-based PCSK9 vaccines have shown a promising prospect of reducing LDL-C. In peptide vaccine (pVax) design, the peptide antigens need to conjugate with carrier protein (CP).

Facile and eco-friendly preparation of super-amphiphilic porous polycaprolactone.

Super-amphiphilic (highly oleophilic and hydrophilic) materials have attracted tremendous interest for fundamental research and potential applications, owing to their unique affinity for both oil and water. In this work, a novel super-amphiphilic porous polycaprolactone (PCL) was fabricated via an efficient and eco-friendly method, in which stearic acid (SA) was used as both a porogen and a dopant precursor. The porous PCL had an interconnected hierarchical pore structure and was capable of absorbing oil and water rapidly.

Facile preparation of degradable multi-arm-star-branched waterborne polyurethane with bio-based tannic acid.

In this research, biodegradable multi-arm-star-branched waterborne polyurethanes (MWPUs) were prepared by incorporation of bio-based material (tannic acid, TA) in the structure of waterborne polyurethanes. The prepared MWPUs were characterized by UV-vis spectrometry and FT-IR spectrometry, confirming the presence of TA in MWPUs. The results of DSC and TGA demonstrated that the incorporation of TA remarkably enhanced the thermal stability of MWPUs.

and controllable synthesis of Ag NPs in tannic acid-based hyperbranched waterborne polyurethanes to prepare antibacterial polyurethanes/Ag NPs composites.

In this research, a simple and facile method was developed for preparation of antibacterial polyurethanes/Ag NPs composites, where tannic acid-based hyperbranched waterborne polyurethanes (THWPU) was employed as both reductant and stabilizer to and controllably synthesize Ag NPs at mild room temperature. The resultant Ag NPs in THWPU was confirmed by UV spectrophotometer, SEM and EDX. The effects of reaction temperature on the properties of the formed Ag NPs were investigated, and the results showed that the formed Ag NPs under room temperature and 80 °C were both spherical, whereas increasing the reaction temperature benefits for promoting the formation of Ag NPs and narrowing the size distribution of the formed Ag NPs.

Synthesis of well-defined star, star-block, and miktoarm star biodegradable polymers based on PLLA and PCL by one-pot azide-alkyne click reaction.

Based on the "arm-first" strategy, ring-opening polymerization (ROP) and one-pot azide-alkyne click reaction, well-defined star-shaped polymers with different architectures have been successfully synthesized, including the star homopolymers four-arm star-shaped polycaprolactone (4sPCL) and four-arm star-shaped poly(l-lactic acid) (4sPLLA), star-block copolymer 4sPCL--PLLA and miktoarm star-shaped copolymer PCLPLLA. The star homopolymers 4sPCL and 4sPLLA were synthesized by a click reaction of an azide small molecule initiator and HC[triple bond, length as m-dash]C-PCL or HC[triple bond, length as m-dash]C-PLLA. The star-block copolymer 4sPCL--PLLA was synthesized by a click reaction of an azide small molecule initiator and the block copolymer HC[triple bond, length as m-dash]C-PCL--PLLA.

Fever-Inspired Immunotherapy Based on Photothermal CpG Nanotherapeutics: The Critical Role of Mild Heat in Regulating Tumor Microenvironment.

Although there have been more than 100 clinical trials, CpG-based immunotherapy has been seriously hindered by complications in the immunosuppressive microenvironment of established tumors. Inspired by the decisive role of fever upon systemic immunity, a photothermal CpG nanotherapeutics (PCN) method with the capability to induce an immunofavorable tumor microenvironment by casting a fever-relevant heat (43 °C) in the tumor region is developed. High-throughput gene profile analysis identifies nine differentially expressed genes that are closely immune-related upon mild heat, accompanied by IL-6 upregulation, a pyrogenic cytokine usually found during fever.

"Minimalist" Nanovaccine Constituted from Near Whole Antigen for Cancer Immunotherapy.

One of the major challenges in vaccine design has been the over dependence on incorporation of abundant adjuvants, which in fact is in violation of the "minimalist" principle. In the present study, a compact nanovaccine derived from a near whole antigen (up to 97 wt %) was developed. The nanovaccine structure was stabilized by free cysteines within each antigen (ovalbumin, OVA), which were tempospatially exposed and heat-driven to form an extensive intermolecular disulfide network.

Harnessing the PEG-cleavable strategy to balance cytotoxicity, intracellular release and the therapeutic effect of dendrigraft poly-l-lysine for cancer gene therapy.

Dendrimer catiomers like dendrigraft poly-l-lysine (DGL) have been very popular vectors for gene delivery recently; however, they generally suffer from serious cytotoxicity for high density of positive charge. PEGylated DGL engineered using the PEG cleavable mechanism (DGL(R)-SS-mPEG) was first developed as a non-viral gene vector for cancer intervention. Cleavable PEGylation of the DGL catiomer in tumor relevant glutathione (GSH) conditions enables us to dramatically decrease the cytotoxicity as well as to promote the intracellular release and expression of the genetic payload.

Disulfide-Bridged Cleavable PEGylation of Poly-L-Lysine for SiRNA Delivery.

Engineered PEG-cleavable catiomers based on poly-L-lysine have been developed as nonviral gene vectors, which have been found to be one of important methods to balance "PEG dilemma." In this protocol, we aim at the standardization of the method and procedure of PEG-cleavable catiomers. Major steps including ring-opening polymerization (ROP) of ε-benzyloxycarbonyl-L-lysine N-carboxyanhydride (zLL-NCA) monomers to yield PEG-cleavable polylysine, examination on bio-stability and bio-efficacy of its gene complexes are described.

Surface-engineered graphene-based nanomaterials for drug delivery.

Graphene, as a newly discovered carbon allotrope, has attracted broad interest and intense attention since its discovery for both fundamental research and a vast array of industrial and biomedical applications. Considerable efforts have been devoted to understanding the nano-bio-interfaces of graphene-based materials for exploring their potential biomedical applications, including drug delivery, biosensing, biomedical imaging, stem cell technology, and photothermal therapy. This review summarizes the current studies on the physiological stability, enhanced permeability and retention (EPR) effect, active targeting and drug carrying capability of graphene-based nanomaterials, and it provides a basic understanding about the mechanisms of drug and gene delivery by these nanomaterials.

Cleavable PEGylation and hydrophobic histidylation of polylysine for siRNA delivery and tumor gene therapy.

Polylysine with cleavable PEGylation and hydrophobic histidylation (mPEG-SS-Lysn-r-Hism) was designed and developed for efficient siRNA delivery and tumor therapy. mPEG-SS-Lysn-r-Hism was used to carry and deliver small interfering RNA (siRNA) for silencing endogenous vascular endothelial growth factor (VEGF) expression and inhibiting tumor growth in HepG2 tumor-bearing mice. In this gene vector, histidine(Bzl) was selected for hydrophobic histidylation for the proton sponge ability of the imidazole ring and hydrophobic benzyl group.

Reduction-cleavable polymeric vesicles with efficient glutathione-mediated drug release behavior for reversing drug resistance.

In the treatment of cancer, multidrug resistance (MDR) has been the major obstacle to the success of chemotherapy. The underlying mechanism relies on the overexpression of drug-efflux transporters that prevent the intracellular transport of the drug. In this study, reduction-cleavable vesicles were designed and developed with efficient glutathione-mediated drug-release behavior for reversing drug resistance.

Pluronic F127 nanomicelles engineered with nuclear localized functionality for targeted drug delivery.

PKKKRKV (Pro-Lys-Lys-Lys-Arg-Lys-Val, PV7), a seven amino acid peptide, has emerged as one of the primary nuclear localization signals that can be targeted into cell nucleus via the nuclear import machinery. Taking advantage of chemical diversity and biological activities of this short peptide sequence, in this study, Pluronic F127 nanomicelles engineered with nuclear localized functionality were successfully developed for intracellular drug delivery. These nanomicelles with the size ~100 nm were self-assembled from F127 polymer that was flanked with two PV7 sequences at its both terminal ends.

Preparation and characterization of new nano-composite scaffolds loaded with vascular stents.

In this study, vascular stents were fabricated from poly (lactide-ɛ-caprolactone)/collagen/nano-hydroxyapatite (PLCL/Col/nHA) by electrospinning, and the surface morphology and breaking strength were observed or measured through scanning electron microscopy and tensile tests. The anti-clotting properties of stents were evaluated for anticoagulation surfaces modified by the electrostatic layer-by-layer self-assembly technique. In addition, nano-composite scaffolds of poly (lactic-co-glycolic acid)/polycaprolactone/nano-hydroxyapatite (PLGA/PCL/nHA) loaded with the vascular stents were prepared by thermoforming-particle leaching and their basic performance and osteogenesis were tested in vitro and in vivo.