CD13-specific ligand facilitates Xanthatin nanomedicine targeting dendritic cells for therapy of refractory allergic rhinitis.

Relapse in Allergic Rhinitis (AR) is triggered by various unclear mechanisms. Xanthium strumarium L. as a traditional folk medicine can inhibit inflammatory responses through multiple mechanisms. Xanthatin (XT) is a bioactive compound derived from Xanthium strumarium L, and we developed a polymeric micelle (PM) that is dendritic cells (DCs)-specific targeting delivery system loading XT (NGR-XT-PM) based on a cyclic peptide moiety (NGR) to render DCs maturation-resistant for therapy of refractory AR. A murine model of AR was employed to investigate the in vivo therapeutic efficiency and relapse rate compared with the commercial product Budesonide. The results showed intranasal administration of NGR-XT-PM presented significant anti-allergy effect with no recurrence, in contrast, all mice treatment with Budesonide relapsed. NGR-XT-PM could effectively reverse the Th1/Th2 imbalance by depleting the serum inflammatory levels (IgE, histamine and IL-4) and DCs surface costimulatory molecules (CD80, CD86 and I-A/I-E), and promote immune tolerance by upregulating the level of Treg cells and reducing the levels of Th2, Th9 and Th17 cells. Furthermore, we appealed to virtual screening of inflammatory targets and found XT blocking the COX-2/PGE2 signaling pathway, which is a key effector in immune responses. These indicated CD13-specific NGR could facilitate XT selectively targeting DCs for efficiently ameliorating refractory rhinitis, and NGR-XT-PM should be a potential anti-AR drug.

[Advance in studies on NGR peptide modified liposome and its anti-tumor performance].

Aspargine-glycine-arginine (NGR)-containing peptides are targeted peptides which can be integrated with CD13 receptors on tumor vascular endothelial cells. NGR peptides are connected to liposomes to obtain NGR peptide-modified liposomes. By intravenous injection of these liposomes, NGR peptides can be combined with CD13 receptors on tumor vascular endothelial cells, position liposomes in tumor tissues, and concentrate drug in liposomes in tumor, so as to enhance the antitumor effect. The article starts with NGR peptides, summarizes definition of NGR, NGR peptide-modified liposomes, strengths and weaknesses of NGR peptide-modified liposomes in antitumor and the latest study orientation of NGR peptide-modified liposomes, and looks into the future of studies on NGR peptide-modified liposomes.

Tumor-specific gene delivery mediated by a novel peptide-polyethylenimine-DNA polyplex targeting aminopeptidase N/CD13.

We have developed a novel polyethylenimine (PEI)-DNA vector formulation that is capable of efficient tumor-specific delivery after intravenous administration to nude mice. To further increase the specificity of delivery, we have attached the peptide CNGRC to the vector, which is specific for aminopeptidase N (CD13). The strategy for coupling this peptide to PEI was based on a novel method involving the strong affinity between phenyl(di)boronic acid (PDBA) and salicylhydroxamic acid (SHA) as well as a polyethylene glycol (PEG) linker to reduce steric hindrance between the vector and the peptide. In vitro assessment of targeting by the CNGRC/PEG/PEI/DNA vector carrying a beta-galactosidase (beta-Gal)-expressing plasmid showed as much as a 5-fold increase in transduction, relative to the untargeted PEG/PEI/DNA-betagal vector, of CD13-positive lung cancer, fibrosarcoma, bladder cancer, and human umbilical vein endothelial cells. Competition with free peptide resulted in up to a 90% reduction in delivery, indicating that gene delivery was specific for CD13-positive cells. Intravenous administration of the CNGRC/PEG/PEI/DNA-betagal vector to nude mice bearing subcutaneous tumors resulted in as much as a 12-fold increase in beta-Gal expression in tumors as compared with expression in either lungs or tumors from animals treated with the original PEI/DNA-betagal vector. In vivo transduction analysis using the CNGRC/PEG/PEI/DNA vector to target the intravenous delivery of a yellow fluorescence protein (YFP)-expressing plasmid to subcutaneous H1299 tumors confirmed delivery of YFP to both tumor cells and tumor endothelial cells. The use of this peptide to further increase tumor-specific delivery mediated by our novel PEI/DNA vector now provides a basis for developing tumor-targeted gene therapies for use in the clinical treatment of cancer.

Effect of soluble porcine aminopeptidase N on antibody production against porcine epidemic diarrhea virus.

A few members of coronavirus group I which includes porcine epidemic diarrhea virus (PEDV) use porcine aminopeptidase N (pAPN) as a cellular receptor. Cellular receptors play an important role in virus attachment and entry. However, the low permissiveness of PEDV to APN-expressing porcine cell lines has made it difficult to elucidate the role of pAPN in vitro. The purpose of this study was to prove whether the treatment of soluble pAPN could enhance the antibody production against PEDV in guinea pigs, rabbits and sows. The animals (20 guinea pigs, 8 rabbits and 20 sows) were divided into 4 groups. Group A was injected intramuscularly (IM) with soluble pAPN at one hour before intramuscular infection of PEDV on the same site, group B for IM simultaneous injection of pAPN and PEDV, and group C for IM injection of PEDV only. Group D served as a control of pAPN treatment or PEDV infection. Antibody production against PEDV was compared among groups at regular intervals. The results suggested that pAPN could enhance the antibody production against PEDV in guinea pigs and rabbits which are free of pAPN, however, the effect of pAPN treatment in sows was not clearly elucidated.