RESUMEN
Despite enormous advancements in its management, cancer is the world's primary cause of mortality. Therefore, tremendous strides were made to produce intelligent theranostics with mitigated side effects and improved specificity and efficiency. Thus, we developed a pH-sensitive theranostic platform composed of dextran immobilized zinc oxide nanoparticles, loaded with doxorubicin and radiolabeled with the technetium-99m radionuclide (99mTc-labelled DOX-loaded ZnO@dextran). The platform measured 11.5 nm in diameter with -12 mV zeta potential, 88% DOX loading efficiency and 98.5% radiolabeling efficiency. It showed DOX release in a pH-responsive manner, releasing 93.1% cumulatively at pH 5 but just 7% at pH 7.4. It showed improved intracellular uptake, which resulted in a high growth suppressive effect against MCF-7 cancer cells as compared to the free DOX. It boasted a 4 times lower IC50 than DOX, indicating its significant anti-proliferative potential (0.14 and 0.55 µg ml-1, respectively). The in vitro biological evaluation revealed that its molecular mode of anti-proliferative action included downregulating Cdk-2, which provoked G1/S cell cycle arrest, and upregulating both the intracellular ROS level and caspase-3, which induced apoptosis and necrosis. The in vivo experiments in Ehrlich-ascites carcinoma bearing mice demonstrated that DOX-loaded ZnO@dextran showed a considerable 4-fold increase in anti-tumor efficacy compared to DOX. Moreover, by utilizing the diagnostic radionuclide (99mTc), the radiolabeled platform (99mTc-labelled DOX-loaded ZnO@dextran) was in vivo monitored in tumor-bearing mice, revealing high tumor accumulation (14% ID g-1 at 1 h p.i.) and reduced uptake in non-target organs with a 17.5 T/NT ratio at 1 h p.i. Hence, 99mTc-labelled DOX-loaded ZnO@dextran could be recommended as a rectified tumor-targeted theranostic platform.
Asunto(s)
Apoptosis , Puntos de Control del Ciclo Celular , Proliferación Celular , Doxorrubicina , Nanomedicina Teranóstica , Óxido de Zinc , Doxorrubicina/farmacología , Doxorrubicina/química , Óxido de Zinc/química , Óxido de Zinc/farmacología , Humanos , Animales , Apoptosis/efectos de los fármacos , Ratones , Concentración de Iones de Hidrógeno , Proliferación Celular/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Células MCF-7 , Nanopartículas/química , Distribución Tisular , Antibióticos Antineoplásicos/farmacología , Antibióticos Antineoplásicos/química , Dextranos/química , Portadores de Fármacos/química , Tecnecio/química , Tamaño de la PartículaRESUMEN
Allantoin increases in different stress conditions and environment such as physical activity, amniotic fluids and oxidative stress. So, we inspired to explore the role of allantoin as a metabolic by-product in health improvement and protection using irradiation as simulator for oxidative stress. Allantoin was injected i.p. (100 mg/kg) in senile male rats in irradiated and non-irradiated groups in comparison to sham operated group. The studied parameters were superoxide dismutase, Glutathione reductase, Glutathione, total antioxidant capacity, collagenase, urea, creatine kinase, alanine transaminase, aspartate aminotransferase, triglycerides, total cholesterol, and HDL and LDL cholesterol. Allantoin in vitro antitumor activity was MTT assayed for some age dependent cancers. Allantoin showed improvement in all in vivo studied oxidative stress parameters. Allantoin showed an increase in lipogenesis was recorded as a hepatic energy targeting muscles. Allantoin improves aging process indicated by its collagenase inhibitory effect. Allantoin showed cytotoxicity against prostate, colon, intestinal ovarian and breast cancers and weak inhibitory against larynx cancer. Allantoin may be the possible mysterious key factor involved in health and aging improvement and cancer protection in stress conditions such as physically activity and radiation hazards.
Asunto(s)
Envejecimiento/efectos de los fármacos , Alantoína/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Animales , Línea Celular Tumoral/efectos de los fármacos , Colagenasas/efectos de los fármacos , Humanos , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Selenium nanoparticles (SeNPs) have become one of the most prospective and promising tools in the course of cancer diagnosis and therapy. Here we describe the synthesis of a novel radioactive platform for tumor imaging using selenium nanoparticles. SeNPs were synthetized using dithionite and glutathione as reducing and capping agent respectively with 5 mmol/L sodium selenite as a precursor and then SeNPs radiolabeled with technetium-99 m, the most common and famous radioactive isotope used for imaging purposes. A characteristic profile for the synthesized SeNPs was performed including size analysis, zeta potential, antioxidant activity, radiochemical yield and in-vivo biodistribution in normal and solid tumor bearing mice. Size analysis showed amorphous SeNP cores of a mean diameter of 21 ± 5 nm with a hydrodynamic size of 43 ± 8 nm and -28 mV zeta potential. The particles also showed a superior antioxidant activity of radical scavenging activity 55.6% according to DPPH assay, in addition, satisfying radiochemical yield up to 97 ± 1.5 was achieved. In vivo studies were applied on male Swiss albino mice that demonstrated a good biodistribution pattern in normal mice with a moderate accumulation in liver at 30 min post injection. Excellent T/NT ratios were obtained in solid tumor bearing mice throughout the experimental time points. The as-synthetized selenium nanoparticles demonstrated surprising and satisfying features which make them promising enough for tumor theranosis.