AFM41a: A Novel PAD2 Inhibitor for Sepsis Treatment-Efficacy and Mechanism.

(PA) infection can cause pneumonia and sepsis by activating peptidyl-arginine deiminase (PAD) and triggering the formation of neutrophil extracellular traps (NETs). Our previous research has elucidated the crucial role of PAD2 in regulating CitH3 production and NETosis signaling following bacterial infection. Therefore, targeting PAD2 with selective inhibitors holds promise for treating PA-induced sepsis.

Nanoemulsion is an effective antimicrobial for methicillin-resistant in infected swine skin burn wounds.

Unlabelled: Burns are one of the most common injuries in both civilian and combat settings and are difficult to treat. This is particularly true when the wounds are infected with antibiotic-resistant bacteria such as methicillin-resistant (MRSA). A new generation of safe, broadly effective, and easily applied anti-infection agents is needed to successfully prevent and treat infections.

A novel intranasal peptide vaccine inhibits non-small cell lung cancer with KRAS mutation.

KRAS mutations occur commonly in the lung and can lead to the development of non-small cell lung cancer (NSCLC). While the mutated KRAS protein is a neoantigen, it usually does not generate an effective anti-tumor immune response on mucosal/epithelial surfaces. Despite this, mutated KRAS remains a potential target for immunotherapy since immune targeting of this protein in animal models has been effective at eliminating tumor cells.

Delicate Hybrid Laponite-Cyclic Poly(ethylene glycol) Nanoparticles as a Potential Drug Delivery System.

The objective of the study was to explore the feasibility of a new drug delivery system using laponite (LAP) and cyclic poly(ethylene glycol) (cPEG). Variously shaped and flexible hybrid nanocrystals were made by both the covalent and physical attachment of chemically homogeneous cyclized PEG to laponite nanodisc plates. The size of the resulting, nearly spherical particles ranged from 1 to 1.

Effective Treatment of Skin Wounds Co-Infected with Multidrug-Resistant Bacteria with a Novel Nanoemulsion.

Wound infections with methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) are particularly difficult to treat and present a great challenge to clinicians. Nanoemulsions (NE) are novel oil-in-water emulsions formulated from soybean oil, water, solvent, and surfactants such as benzalkonium chloride (BZK). An optimal ratio of those components produces nanometer-sized particles with the positive-charged surfactant at their oil-water interface.

Dendrimer-based posaconazole nanoplatform for antifungal therapy.

We examined formulating a new antifungal agent, posaconazole (POS) and its derivatives, with different molecular vehicles. Several combinations of drug and carrier molecules were synthesized, and their antifungal activities were evaluated against . Posaconazole and four of its derivatives were conjugated to either generation 5 (G5) dendrimers or partially modified G5 dendrimers.

Functionalized nanoparticles with targeted antibody to enhance imaging of breast cancer in vivo.

Background: Targeted contrast nanoparticles for breast tumor imaging facilitates early detection and improves treatment efficacy of breast cancer. This manuscript reports the development of an epidermal growth factor receptor-2 (HER-2) specific, bi-modal, dendrimer conjugate to enhance computed tomography (CT) and magnetic resonance imaging (MRI) of HER-2-positive breast cancer. This material employs generation 5 poly(amidoamine) dendrimers, encapsulated gold nanoparticles, chelated gadolinium, and anti-human HER-2 antibody to produce the nanoparticle contrast agent.

A novel combination of intramuscular vaccine adjuvants, nanoemulsion and CpG produces an effective immune response against influenza A virus.

Background: Vaccination is the most effective approach to prevent infection with highly pathogenic avian influenza (HPAI). Adjuvants are often used to induce effective immune responses and overcome the immunological weakness of recombinant HPAI antigens. Given the logistical challenges of immunization to HPAI during pandemic situations, vaccines administered via the intramuscular (I.

Nanoemulsion as an Effective Treatment against Human-Pathogenic Fungi.

Infections triggered by pathogenic fungi cause a serious threat to the public health care system. In particular, an increase of antifungal drug-resistant fungi has resulted in difficulty in treatment. A limited variety of antifungal drugs available to treat patients has left us in a situation where we need to develop new therapeutic approaches that are less prone to development of resistance by pathogenic fungi.

Recombinant H5 hemagglutinin adjuvanted with nanoemulsion protects ferrets against pathogenic avian influenza virus challenge.

Background: Highly pathogenic H5N1 influenza viruses remain a pandemic risk to the world population. Although vaccines are the best solution to prevent this threat, a more effective vaccine for H5 strains of influenza has yet to be developed. All existing vaccines target only serum antibody against influenza as the primary outcome, while mucosal immunity has not been addressed.

Nanoemulsion is an effective antimicrobial for methicillin-resistant Staphylococcus aureus in infected wounds.

Aim: To develop NB-201, a nanoemulsion compound, as a novel microbicidal agent against methicillin-resistant Staphylococcus aureus (MRSA) infection, which is a common threat to public health but with limited therapeutic options.

Materials & Methods: NB-201 was tested in in vitro and in vivo murine and porcine models infected with MRSA.

Results: Topical treatment of MRSA-infected wounds with NB-201 significantly decreased bacterial load and had no toxic effects on healthy skin tissues.

Screening of Nanoemulsion Formulations and Identification of NB-201 as an Effective Topical Antimicrobial for Staphylococcus aureus in a Mouse Model of Infected Wounds.

Despite advances in antimicrobial therapies, wound infection remains a global public health concern. We aimed to formulate and assess various nanoemulsions (NEs) for potential effectiveness as stable antimicrobial agents suitable for topic application. A total of 106 NEs were developed that varied with respect to nonionic and cationic surfactants.

Dendrimer antibody conjugate to target and image HER-2 overexpressing cancer cells.

Although many breast and lung cancers overexpress human epidermal growth factor receptor-2 (HER-2), no methods currently exist for effective and early detection of HER-2-positive cancers. To address this issue, we designed and synthesized dendrimer-based novel nano-imaging agents that contain gold nanoparticles (AuNPs) and gadolinium (Gd), conjugated with the humanized anti-HER-2 antibody (Herceptin). Generation 5 (G5) polyamidoamine (PAMAM) dendrimers were selected as the backbone for the nano-imaging agents due to their unique size, high ratio of surface functional groups and bio-functionality.

Modified Nanoemulsions with Iron Oxide for Magnetic Resonance Imaging.

A nanoemulsion (NE) is a surfactant-based, oil-in-water, nanoscale, high-energy emulsion with a mean droplet diameter of 400-600 nm. When mixed with antigen and applied nasally, a NE acts as a mucosal adjuvant and induces mucosal immune responses. One possible mechanism for the adjuvant effect of this material is that it augments antigen uptake and distribution to lymphoid tissues, where the immune response is generated.

Overexpression of BID in thyroids of transgenic mice increases sensitivity to iodine-induced autoimmune thyroiditis.

Background: BID functions as a bridge molecule between death-receptor and mitochondrial related apoptotic pathways to amplify apoptotic signaling. Our previous studies have demonstrated a substantial increase in BID expression in primary normal thyroid epithelia cells treated with inflammatory cytokines, including the combination of IFNγ and IL-1β or IFNγ and TNFα. The aim of this study was to determine whether an increase in BID expression in thyroid can induce autoimmune thyroiditis.

Characterization of a novel transgenic mouse tumor model for targeting HER2+ cancer stem cells.

HER2 is an oncogenic tumor-associated antigen overexpressed in 20-25% of breast cancers, which is associated with increased invasion, metastasis of the disease and resistance to therapy. Recent studies have further shown that HER2 can increase the population of breast cancer stem cells (BCSCs). However, there is currently no in vivo model for the study of HER2(+) BCSCs.

Formulation and characterization of nanoemulsion intranasal adjuvants: effects of surfactant composition on mucoadhesion and immunogenicity.

The development of effective intranasal vaccines is of great interest due to their potential to induce both mucosal and systemic immunity. Here we produced oil-in-water nanoemulsion (NE) formulations containing various cationic and nonionic surfactants for use as adjuvants for the intranasal delivery of vaccine antigens. NE induced immunogenicity and antigen delivery are believed to be facilitated through initial contact interactions between the NE droplet and mucosal surfaces which promote prolonged residence of the vaccine at the site of application, and thus cellular uptake.

Induction of immune tolerance in mice with a novel mucosal nanoemulsion adjuvant and self-antigen.

Aim: The aim of this study was to investigate the impact of a novel nanoemulsion (NE) adjuvant, a soybean oil emulsion, on autoimmune response. To this end, we used murine thyroglobulin (mTg)-induced experimental autoimmune thyroiditis in mice as a study model.

Materials & Methods: Mice received NE or NE + mTg by nasal delivery.

Facile one-pot preparation, surface functionalization, and toxicity assay of APTS-coated iron oxide nanoparticles.

We report a facile approach to synthesizing 3-aminopropyltrimethoxysilane (APTS)-coated magnetic iron oxide (Fe(3)O(4)@APTS) nanoparticles (NPs) with tunable surface functional groups for potential biomedical applications. The Fe(3)O(4) NPs with a mean diameter of 6.5 nm were synthesized by a hydrothermal route in the presence of APTS.

Influence of dendrimer surface charge on the bioactivity of 2-methoxyestradiol complexed with dendrimers.

We report the complexation of a potential anticancer agent 2-methoxyestradiol (2-ME) with generation 5 (G5) poly(amidoamine) dendrimers having different surface functional groups for therapeutic applications. The complexation experiment shows that approximately 6-8 drug molecules can be complexed with one dendrimer molecule regardless the type of the dendrimer terminal groups. The bioactivity of 2-ME complexed with dendrimers was found to be significantly dependent on the surface charge of G5 dendrimers.

Comparison of the internalization of targeted dendrimers and dendrimer-entrapped gold nanoparticles into cancer cells.

Dendrimer-based nanotechnology significantly advances the area of targeted cancer imaging and therapy. Herein, we compared the difference of surface acetylated fluorescein isocyanate (FI) and folic acid (FA) modified generation 5 (G5) poly(amidoamine) dendrimers (G5.NHAc-FI-FA), and dendrimer-entrapped gold nanoparticles with similar modifications ([(Au(0))(51.

Targeting and detecting cancer cells using spontaneously formed multifunctional dendrimer-stabilized gold nanoparticles.

We develop a facile approach to fabricating multifunctional dendrimer-stabilized gold nanoparticles (Au DSNPs) for cancer cell targeting and imaging. In this work, amine-terminated generation 5 (G5) poly(amidoamine) (PAMAM) dendrimers pre-functionalized with folic acid (FA) and fluorescein isothiocyanate (FI) are complexed with Au(III) ions, followed by acetylation of the amine groups on the dendrimer surfaces. This one-step process leads to the spontaneous formation of 6 nm-sized Au nanoparticles stabilized by multifunctional dendrimers bearing both targeting and imaging functionalities.

Multifunctional dendrimer-modified multiwalled carbon nanotubes: synthesis, characterization, and in vitro cancer cell targeting and imaging.

Carbon nanotubes hold great promise for their use as a platform in nanomedicine, especially in drug delivery, medical imaging, and cancer targeting and therapeutics. Herein, we present a facile approach to modifying carbon nanotubes with multifunctional poly(amidoamine) (PAMAM) dendrimers for cancer cell targeting and imaging. In this approach, fluorescein isothiocyanate (FI)- and folic acid (FA)-modified amine-terminated generation 5 (G5) PAMAM dendrimers (G5·NH(2)-FI-FA) were covalently linked to acid-treated multiwalled carbon nanotubes (MWCNTs), followed by acetylation of the remaining primary amine groups of the dendrimers.

Therapeutic efficacy of 2-methoxyestradiol microcrystals encapsulated within polyelectrolyte multilayers.

Development of a novel formulation of anticancer drugs to improve their water-solubility and bioavailability remains a great challenge. Herein, the potential anticancer agent 2-methoxyestradiol (2-ME) was selected as a model drug and was encapsulated within polyelectrolyte (PE) multilayers by layer-by-layer deposition of oppositely charged PEs onto the drug microcrystal surfaces. Cell viability and morphology observation of two cell lines reveal that the PE multilayer-encapsulated 2-ME microcrystals markedly decrease the cell viability, displaying similar inhibitory effect to that of the conventional formulation of 2-ME dissolved in ethanol.