In vivo gene delivery mediated by non-viral vectors for cancer therapy.

Gene therapy by expression constructs or down-regulation of certain genes has shown great potential for the treatment of various diseases. The wide clinical application of nucleic acid materials dependents on the development of biocompatible gene carriers. There are enormous various compounds widely investigated to be used as non-viral gene carriers including lipids, polymers, carbon materials, and inorganic structures. In this review, we will discuss the recent discoveries on non-viral gene delivery systems. We will also highlight the in vivo gene delivery mediated by non-viral vectors to treat cancer in different tissue and organs including brain, breast, lung, liver, stomach, and prostate. Finally, we will delineate the state-of-the-art and promising perspective of in vivo gene editing using non-viral nano-vectors.

Synthesis, Spectral Characterization, DNA/ Protein Binding, DNA Cleavage, Cytotoxicity, Antioxidative and Molecular Docking Studies of Cu(II)Complexes Containing Schiff Base-bpy/Phen Ligands.

Ternary Cu(II) complexes [Cu(II)(L)(bpy)Cl] 1, [Cu(II)(L)(Phen)Cl] 2 [L = 2,3-dimethyl-1-phenyl-4(2 hydroxy-5-methyl benzylideneamino)-pyrazol-5-one, bpy = 2,2' bipyridine, phen =1,10 phenanthroline) were synthesized and characterized by elemental analyses, UV-Visible, FT-IR, ESR, Mass, thermogravimetric and SEM EDAX techniques. The complexes exhibit octahedral geometry. The interaction of the Cu(II) with cailf thymus DNA (CT-DNA) was explored by using absorption and fluorescence spectroscopic methods. The results revealed that the complexes have an affinity constant for DNA in the order of 104 M-1 and mode of interaction is intercalative mode. The DNA cleavage study showed that the complexes cleaved DNA without any external agent. The interaction of Cu(II) complexes with bovine serum albumin (BSA) was also studied using absorption and fluorescence techniques. The cytotoxic activity of the Cu(II) complexes was probed in HeLa (human breast adenocarcinoma cell line), B16F10 (Murine melanoma cell line) and HEPA1-6 celllines, complex 1 has good cytotoxic activity which is comparable with the doxarubicin drug, with IC50 values ranging from 3 to 12.6 µM. A further molecular docking technique was employed to understand the binding of the complexes towards the molecular target DNA. Investigation of the antioxidative properties showed that the metal complexes have significant radical scavenging activity potency against DPPH radical.

Liposomally encapsulated CDC20 siRNA inhibits both solid melanoma tumor growth and spontaneous growth of intravenously injected melanoma cells on mouse lung.

Cell division cycle homologue 20 (CDC20), a key cell cycle regulator required for the completion of mitosis in organisms from yeast to human, is highly expressed in several carcinomas. Recent studies have shown that specific knockdown of CDC20 expression is capable of significantly inhibiting the growth of human pancreatic carcinoma cells. However, preclinical studies aimed at demonstrating the therapeutic potential of CDC20 siRNA in combating tumor growth has not yet been reported. Herein, in a syngeneic C57BL/6J mouse tumor model, we show that intraperitoneal administration of a 19-bp synthetic CDC20 siRNA encapsulated within liposomes of guanidinylated cationic amphiphile with stearyl tails inhibits solid melanoma (B16F10) tumor growth. In addition, using a spontaneous lung metastasis model in C57BL/6J mice, we show that intravenous administration of the same liposomally encapsulated 19-bp synthetic CDC20 siRNA inhibits B16F10 melanoma growth on mouse lung. Liposomally bound CDC20 siRNA was found to be efficient in silencing the expression of CDC20 in B16F10 cells at both protein and mRNA levels. Findings in the flow cytometric studies confirmed the presence of significantly enhanced populations of G2/M phase in cells treated with liposomally bound CDC20 siRNA. To the best of our knowledge, the present findings demonstrate, for the first time, systemic use of CDC20 siRNA in inhibiting mouse tumor growth.