Multiple myeloma (MM) is a clonal disease of plasma cells that reside in the bone marrow (BM). MM is an incurable disease; thus, screening for novel anti-myeloma drugs remains critically important. We recently described a silica nanoparticle-based snake venom delivery model that targets cancer cells, but not normal cells. Using this model, we demonstrated a strong enhancement of the antitumor activity of snake venom extracted from Walterinnesia aegyptia (WEV) in two breast carcinoma cell lines when the venom was combined with silica nanoparticles (WEV+NP). In the present study, we aimed to delineate the in vivo therapeutic efficacy of WEV+NP in an MM-bearing experimental nude mouse model. We found that treatment with WEV+NP or WEV alone significantly inhibited tumor growth compared to treatment with NP or vehicle. WEV+NP- and WEV-treated cancer cells exhibited marked elevations in oxidative stress and robust reductions in the levels of interleukin-6 (IL-6) and B cell-activating factor (BAFF). WEV+NP also decreased the surface expression of the chemokine receptors CXCR3, CXCR4 and CXCR6 to a greater extent than WEV alone, and WEV+NP subsequently reduced migration in response to the cognate ligands CXCL10, CXCL12 and CXCL16. Furthermore, we found that WEV+NP strongly inhibited insulin-like growth factor 1 (EGF-1)- and IL-6-mediated MM cell proliferation, altered the cell cycle and enhanced the induction of apoptosis of MM cells. In addition, the results of treatment with WEV+NP or WEV alone revealed that the combination of WEV with NP robustly decreased the expression of cyclin D1, Bcl-2 and the phosphorylation of AKT; increased the expression of cyclin B1; altered the mitochondrial membrane potential; increased the activity of caspase-3, -8 and -9; and sensitized MM cells to growth arrest and apoptosis. Our data reveal the therapeutic potential of the nanoparticle-sustained delivery of snake venom to fight cancer cells.

urea as a combustion fuel. The fabrication was carried out by refluxing a mixture of cobalt nitrate and
urea followed by calcination, for 3 h in static air atmosphere, at 400 °C. The thermal genesis of the Co3O4
was explored by means of thermogravimetric and differential thermal analyses in air atmosphere in the
temperature range 25-1000 °C. X-ray diffraction, Fourier transform infrared spectra, and scanning electron
microscopy were used to characterize the structure and morphology of the Co3O4. The obtained results
conrmed that the resulting oxides were comprised of pure single-crystalline Co3O4 nanoparticles. Moreover,
various comparison experiments showed that several experimental parameters, such as the reflux
time and the urea/cobalt nitrate molar ratio, play important roles in the crystallite size as well as the morphological
control of Co3O4 powders. Consequently, the minimum crystallite size can be obtained at 12 h
reflux and a urea/cobalt nitrate molar ratio of 5.

urea as a combustion fuel. The fabrication was carried out by refluxing a mixture of cobalt nitrate and
urea followed by calcination, for 3 h in static air atmosphere, at 400 °C. The thermal genesis of the Co3O4
was explored by means of thermogravimetric and differential thermal analyses in air atmosphere in the
temperature range 25-1000 °C. X-ray diffraction, Fourier transform infrared spectra, and scanning electron
microscopy were used to characterize the structure and morphology of the Co3O4. The obtained results
conrmed that the resulting oxides were comprised of pure single-crystalline Co3O4 nanoparticles. Moreover,
various comparison experiments showed that several experimental parameters, such as the reflux
time and the urea/cobalt nitrate molar ratio, play important roles in the crystallite size as well as the morphological
control of Co3O4 powders. Consequently, the minimum crystallite size can be obtained at 12 h
reflux and a urea/cobalt nitrate molar ratio of 5.

urea as a combustion fuel. The fabrication was carried out by refluxing a mixture of cobalt nitrate and
urea followed by calcination, for 3 h in static air atmosphere, at 400 °C. The thermal genesis of the Co3O4
was explored by means of thermogravimetric and differential thermal analyses in air atmosphere in the
temperature range 25-1000 °C. X-ray diffraction, Fourier transform infrared spectra, and scanning electron
microscopy were used to characterize the structure and morphology of the Co3O4. The obtained results
conrmed that the resulting oxides were comprised of pure single-crystalline Co3O4 nanoparticles. Moreover,
various comparison experiments showed that several experimental parameters, such as the reflux
time and the urea/cobalt nitrate molar ratio, play important roles in the crystallite size as well as the morphological
control of Co3O4 powders. Consequently, the minimum crystallite size can be obtained at 12 h
reflux and a urea/cobalt nitrate molar ratio of 5.

Cobalt oxide nano-particles were prepared by combustion method using urea as a combustion fuel. The
effects of calcination temperature, 350–1000 ◦C, on the physicochemical, surface and catalytic properties
of the prepared Co3O4 nano-particles were studied. The products were characterized by thermal
analyses (TGA & DTA), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning
electron microscopy (SEM), and transmission electron microscopy (TEM) techniques. Textural features
of the obtained catalysts were investigated using nitrogen adsorption at
−196 ◦C. X-ray diffraction confirmed
that the resulting oxide was pure single-crystalline Co3O4 nano-particles. Transmission electron
microscopy indicating that, the crystallite size of Co3O4 nano-crystals was in the range of 8–34 nm. The
catalytic activities of prepared nano-crystalline Co3O4 catalysts were tested for H2O2 decomposition at
35–50 ◦C temperature range. Experimental results revealed that, the catalytic decomposition of H2O2
decreases with increasing the calcination temperature. This was correlated with the observed particle
size increase accompanying the calcination temperature rise.

Cobalt oxide nano-particles were prepared by combustion method using urea as a combustion fuel. The
effects of calcination temperature, 350–1000 ◦C, on the physicochemical, surface and catalytic properties
of the prepared Co3O4 nano-particles were studied. The products were characterized by thermal
analyses (TGA & DTA), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning
electron microscopy (SEM), and transmission electron microscopy (TEM) techniques. Textural features
of the obtained catalysts were investigated using nitrogen adsorption at
−196 ◦C. X-ray diffraction confirmed
that the resulting oxide was pure single-crystalline Co3O4 nano-particles. Transmission electron
microscopy indicating that, the crystallite size of Co3O4 nano-crystals was in the range of 8–34 nm. The
catalytic activities of prepared nano-crystalline Co3O4 catalysts were tested for H2O2 decomposition at
35–50 ◦C temperature range. Experimental results revealed that, the catalytic decomposition of H2O2
decreases with increasing the calcination temperature. This was correlated with the observed particle
size increase accompanying the calcination temperature rise.

Cobalt oxide nano-particles were prepared by combustion method using urea as a combustion fuel. The
effects of calcination temperature, 350–1000 ◦C, on the physicochemical, surface and catalytic properties
of the prepared Co3O4 nano-particles were studied. The products were characterized by thermal
analyses (TGA & DTA), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning
electron microscopy (SEM), and transmission electron microscopy (TEM) techniques. Textural features
of the obtained catalysts were investigated using nitrogen adsorption at
−196 ◦C. X-ray diffraction confirmed
that the resulting oxide was pure single-crystalline Co3O4 nano-particles. Transmission electron
microscopy indicating that, the crystallite size of Co3O4 nano-crystals was in the range of 8–34 nm. The
catalytic activities of prepared nano-crystalline Co3O4 catalysts were tested for H2O2 decomposition at
35–50 ◦C temperature range. Experimental results revealed that, the catalytic decomposition of H2O2
decreases with increasing the calcination temperature. This was correlated with the observed particle
size increase accompanying the calcination temperature rise.