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Mahmoudi M.,Tehran University of Medical Sciences | Mahmoudi M.,Pasteur Institute of Iran | Serpooshan V.,Stanford University
ACS Nano | Year: 2012

The combination of patients with poor immune system, prolonged exposure to anti-infective drugs, and cross-infection has given rise to nosocomial infections with highly resistant pathogens, which is going to be a growing threat so termed "antibiotic resistance". Due to their significant antimicrobial activity, silver nanoparticles are recognized as a promising candidate to fight against resistant pathogens; however, there are two major shortcomings with these nanoparticles. First, the silver nanoparticles are highly toxic to the healthy cells; second, due to the protection offered by the biofilm mode of growth, the silver nanoparticles cannot eradicate bacterial biofilms. In order to overcome these limitations, this study introduces a new class of engineered multimodal nanoparticles comprising a magnetic core and a silver ring with a ligand gap. The results indicated promising capability of the designed multimodal nanoparticles for high-yield antibacterial effects and eradication of bacterial biofilms, while the particles were completely compatible with the cells. Utilizing a gold ring as an intermediate coating on the produced nanoparticles may exploit new opportunities for theranosis applications. This will require special consideration in future works. © 2012 American Chemical Society.


Bolhassani A.,Pasteur Institute of Iran
Biochimica et biophysica acta | Year: 2011

Cell penetrating peptides (CPPs) are short amphipathic and cationic peptides that are rapidly internalized across cell membranes. They can be used to deliver molecular cargo, such as imaging agents (fluorescent dyes and quantum dots), drugs, liposomes, peptide/protein, oligonucleotide/DNA/RNA, nanoparticles and bacteriophage into cells. The utilized CPP, attached cargo, concentration and cell type, all significantly affect the mechanism of internalization. The mechanism of cellular uptake and subsequent processing still remains controversial. It is now clear that CPP can mediate intracellular delivery via both endocytic and non-endocytic pathways. In addition, the orientation of the peptide and cargo and the type of linkage are likely important. In gene therapy, the designed cationic peptides must be able to 1) tightly condense DNA into small, compact particles; 2) target the condensate to specific cell surface receptors; 3) induce endosomal escape; and 4) target the DNA cargo to the nucleus for gene expression. The other studies have demonstrated that these small peptides can be conjugated to tumor homing peptides in order to achieve tumor-targeted delivery in vivo. On the other hand, one of the major aims in molecular cancer research is the development of new therapeutic strategies and compounds that target directly the genetic and biochemical agents of malignant transformation. For example, cell penetrating peptide aptamers might disrupt protein-protein interactions crucial for cancer cell growth or survival. In this review, we discuss potential functions of CPPs especially for drug and gene delivery in cancer and indicate their powerful promise for clinical efficacy. Copyright © 2011 Elsevier B.V. All rights reserved.


The embodiments herein provide a dipstick nano-biosensor for diagnosing Plasmodium vivax and Plasmodium falciparum. The dipstick biosensor comprises a backing plate coated with a cellulose membrane, nitrocellulose membrane and fibreglass. Gold nanoparticles coated with antidigoxigenin are immobilized on the dipstick along with probes comprising strptavidin, texas red, biotin and fluorescein. The dipstick biosensor has three regions comprising a wicking pad, conjugate pad having two control lines and two test lines and an absorbent pad. The first Control line comprises nitrocellulose membrane coated with antifluorescein. The second control line comprises nitrocellulose membrane coated with anti anti-sheep. The first test line comprises nitrocellulose membrane coated with streptavidin conjugated to biotin. The second test line comprises nitrocellulose membrane coated with anti texas red. The two test lines help to confirm the diagnostic results.


The embodiments herein provide a composition and a method of synthesizing a composition comprising an aliphatic amino acid biosynthesis inhibitor having an antifungal activity. The composition comprises 2-oxo-2H-chromen-7-yl propiolate, diethyl-hex-2-en-4-yne-dioate and dinonyl-hex-2-en-4-yne-dioate. The composition inhibits a biosynthesis of an aliphatic amino acid in a fungal biological system. The aliphatic amino acid is selected from a group consisting of leucine, isoleucine and valine. The composition is used with a concentration of 0-200 g/ml. The method comprises mixing solutions of dicyclohexylcarbodiimide (DCC) and Dimethylaminopyridine (DMAP) with alcohol, acetylene carboxylic acid and dichloromethane to obtain a mixture which is stirred filtered and washed with ether. The solvents are evaporated to obtain a residue that is dissolved in dichloromethane and stirred with a catalyst. The extra solvents are evaporated to obtain the derivative compound and purified by silica gel column chromatography.


The present invention discloses the thrombolytic therapy by t-PA or CT-b for the treatment of the acute myocardial infarction. A chimeric truncated form of t-PA or CT-b is designed and expressed in Pichia pastoris. The CT-b includes desmoteplase finger domain, human EGF, kringle 1 and protease domain. The human kringle 2 domain is removed in CT-b to make it structurally and functionally similar to desmoteplase. The fibrin specificity or the catalytic activity is 1560 times more in the presence of fibrin. The CT-b also shows 1.2 fold higher resistances to PAI-1 enzyme. As the kringle domain is considered as one of the binding sites for PAI-1, the deletion along with amino acid substitution in protease domain contributes to prolonged half-life. Further the activity of the CT-b is intact after exposure to PAI-1. In other words CT-b is inhibited 44% less than t-PA by PAI-1 enzyme, demonstrating improved half life.


The various embodiments herein provide a chimeric truncated and mutant variant of a tissue plasminogen activator (t-pa) and a method for preparing the same. According to an embodiment herein, the mutant variant comprises a signal sequence domain, followed by a chimeric tetrapeptide, followed by a tripeptide, followed by a kringle 2 domain, followed by a serine protease domain and a substituted amino acids at position 128-131. The substituted amino acids are AAAA (SEQ ID NO: 3) amino acids. The chimeric tetrapeptide is Gly-His-Arg-Pro (SEQ ID NO: 1). The chimeric tetrapeptide is at a position of 36 to 39 amino acid of the mutant variant. The tripeptide is Ser-Tyr-Glu. According to an embodiment herein, a chimeric truncated and mutant variant of a tissue plasminogen activator comprises a native t-pa deleted with Finger domain, a Growth Factor domain and a Kringle 1 domain, a chimeric tetrapeptide and a substituted amino acids at a position of 128-131.


The present invention discloses a thrombolytic therapy for acute myocardial infarction by t-PA. A chimeric truncated form of t-PA is designed and expressed in Pichia pastoris. The new variant t-PA comprises of a finger domain of Desmoteplase, an epidermal growth factor (EGF) domain, a kringle 1 domain, a kringle 2 domain in which the lysine binging site is deleted, and a protease domain where the four amino acids lysine 296, arginine 298, arginine 299, and arginine 304 are substituted by aspartic acid. The chimeric t-PA shows has increased activity of 14 fold in presence of fibrin. The t-PA shows 10-fold increased potency than commercially available full length t-PA (Actylase) and provides 1.2 fold greater affinity to fibrin. Further a residual activity of only 68% is observed after incubation of Actylase with PAI-1 and 91% residual activity for t-PA. The t-PA variant is acceptable plasminogen activator with enhanced biochemical properties.


The various embodiments herein provide a gold coated SPIONs with jagged surface. The gold coated SPIONs have a core and a shell. The core is a SPION molecule and the shell is a jagged gold layer. A non-uniform polymeric gap exists between the core and the shell. The embodiments also provide a method of producing the jagged gold coated SPIONs by mixing a colloidal dispersion of SPIONs with pH sensitive polymers. Adding a gold salt to the above mixture and reducing the gold salt to form jagged gold coated SPIONs.


The various embodiments herein provide super paramagnetic iron oxide nanoparticles (SPIONs). The SPIONs have a plurality of metallic coatings and plurality of polymeric gaps. The embodiments herein also provide a method of synthesizing the SPIONs with metallic rings and polymeric gaps. The metallic coatings form a ring like structure on the outer surface of the SPION. The SPION has a size of 13 nm. The ring has a thickness of 2-3 nm. The rings are one or more in number. The polymeric gaps have a thickness of 3-5 nm. The polymeric gaps are one or more in number. The method involves mixing the SPIONs with a plurality of polymers and then forming a metallic ring on the outer surface of the SPIONs. The SPIONs have anti-bacterial properties and stop a growth of bacterial biofilms. The SPIONs also have SERS properties.


The embodiments herein discloses a vaccine against urinary tract infection (UTI). The flagellin (FliC) of enteroaggregative Escherichia coli is fused to FimH derived from uropathogenic Escherichia coli. The interaction of FliC and FimH with Toll-like receptor 5 (TLR-5) is analyzed in silico by docking protocols. The fused protein obtained after docking studies are subjected to cloning and expression in a vector. The recombinant vaccine expressed by the vector is purified. The recombinant vaccine has a size of 1200 bp. The ability of the recombinant vaccine FliCA-FimH-FliCB and the truncated form is analyzed by immunizing the mice. The result illustrate that the truncated forms are capable of inducing T helper 1 and T helper 2 cell response. It is also illustrated that the fusion vaccine induces a strong cellular and humoral immune response.

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