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Vaccination has been one of the most successful breakthroughs in medical history. In recent years, epitope-based subunit vaccines have been introduced as a safer alternative to traditional vaccines. However, they suffer from limited immunogenicity. Nanotechnology has shown value in solving this issue. Different kinds of nanovaccines have been employed, among which virus-like nanoparticles (VLPs) and self-assembled peptide nanoparticles (SAPNs) seem very promising. Recently, SAPNs have attracted special interest due to their unique properties, including molecular specificity, biodegradability, and biocompatibility. They also resemble pathogens in terms of their size. Their multivalency allows an orderly repetitive display of antigens on their surface, which induces a stronger immune response than single immunogens. In vaccine design, SAPN self-adjuvanticity is regarded an outstanding advantage, since the use of toxic adjuvants is no longer required. SAPNs are usually composed of helical or β-sheet secondary structures and are tailored from natural peptides or de novo structures. Flexibility in subunit selection opens the door to a wide variety of molecules with different characteristics. SAPN engineering is an emerging area, and more novel structures are expected to be generated in the future, particularly with the rapid progress in related computational tools. The aim of this review is to provide a state-of-the-art overview of self-assembled peptide nanoparticles and their use in vaccine design in recent studies. Additionally, principles for their design and the application of computational approaches to vaccine design are summarized. [ABSTRACT FROM AUTHOR]

A novel lipopolymer based system was designed and characterized for cellular delivery of anti-VEGF siRNA in SKBR-3 breast tumor cell line. Polyamidoamine (PAMAM) dendrimers of low generations (G1, G2 and G3) were incorporated into polyethylene glycol (PEG)-stabilized liposomes by following the consecutive steps: (a) synthesis of the cholesterol conjugates (40% molar ratio of cholesterol to primary amines of PAMAM), (b) incorporation of the conjugates in liposome by lipid mixing and (c) microencapsulation of the siRNA using the ethanol drop method. The cholesterol conjugates of PAMAM dendrimers (G1-Chol 40%, G2-Chol 40% and G3-Chol 40% ) formed self assembly with low CMC values (<11 μg/ml). Not only did G2-Chol 40% show the highest lipid mixing among the cholesterol conjugates, but also, had the lowest leakage of encapsulated carboxyfluorescein tracer. Various N(amine))/L(lipid)/P(phosphate) mole ratios were investigated for siRNA condensation by ethidium bromide dye exclusion assay. The optimum N/L/P ratio of 20:33:10 was chosen for microencapsulation of anti-VEGF siRNA by ethanol drop method, showing particle size of 130 nm, zeta-potential of +4 mV, siRNA loading efficiency and capacity of 96% and 13 wt%, and high stability against heparin sulfate (extracellular matrix). TEM shows uniform and discrete oligo- or multi-lamellar vesicular structures. The liposome incorporating G2-Chol 40% was successfully internalized into SKBR-3 cells mainly through clathrin-mediated endocytosis, which was able to escape from endosomes and showed a significantly higher sequence-specific inhibition of VEGF expression and cell growth than the respective G2-Chol 40% /siRNA dendriplexes. Importantly, the cytotoxicity decreased with incorporation of G2-Chol 40% in the liposomes. [ABSTRACT FROM AUTHOR]

The current study deals with the production of l -methioninase from newly isolated bacterium Alcaligenes spp. via submerged fermentation. The statistical methods of one factor at a time (OFAT) and response surface methodology were used to optimize the nutritional and cultivation factors for the production of l -methioninase by Alcaligenes sp MT-B. The regression models depicted considerably high R 2 values of 0.87% for l -methioninase activities, signifying that they are suitable for forecasting associations between lactose, yeast extract, pH and temperature. In accordance with the model, the optimum condition for l -methioninase production were yeast extract 0.2%; lactose 0.75%, pH 6 and temperature 34.6 °C. These forecasted conditions were confirmed by validation trials. In the optimized condition Alcaligenes sp MT-B produced l -methioninase with the activity of 13.06 U/ml which is 1.4 times superior to that produced in initial fermentation condition. Hence, this statistical technique enabled fast identification and combination of key medium factors for Alcaligenes sp MT-B, resulted in the high l -methioninase production. • Introducing new bacterium genus (Alcaligenes sp. MT-B) for l -methioninase production. • Optimization of factors for l -methioninase production. • l -methioninase could be used for cancer therapy. [ABSTRACT FROM AUTHOR]