dioleoyl-phosphatidylethanolamine and Prostatic-Neoplasms

Herein, we describe the preparation of liposomes with folate-targeting properties for the encapsulation of anti-sarcosine antibodies (antisarAbs@LIP) and sarcosine (sar@LIP). The competitive inhibitory effects of exogenously added folic acid supported the role of folate targeting in liposome internalization. We examined the effects of repeated administration on mice PC-3 xenografts. Sar@LIP treatment significantly increased tumor volume and weight compared to controls treated with empty liposomes. Moreover, antisarAbs@LIP administration exhibited a mild antitumor effect. We also identified differences in gene expression patterns post-treatment. Furthermore, Sar@LIP treatment resulted in decreased amounts of tumor zinc ions and total metallothioneins. Examination of the spatial distribution across the tumor sections revealed a sarcosine-related decline of the MT1X isoform within the marginal regions but an elevation after antisarAbs@LIP administration. Our exploratory results demonstrate the importance of sarcosine as an oncometabolite in PCa. Moreover, we have shown that sarcosine can be a potential target for anticancer strategies in management of PCa.

Topics: Animals; Antibodies, Monoclonal; Cell Line, Tumor; Disease Models, Animal; Dose-Response Relationship, Drug; Folic Acid; Humans; Liposomes; Male; Metallothionein; Mice; Models, Biological; Phosphatidylethanolamines; Prostatic Neoplasms; Sarcosine; Tumor Burden; Xenograft Model Antitumor Assays; Zinc

In the study we made use of DOTAP (1,2-dioleoyl-3-trimethylammonium), DOPE (1,2-dioleoyl-snglycero-3-phosphoethanolamine) and PEG-PE (polyethylene glycol- polyethylene) to make cationic PEG-liposomes by ultrasonic dispersion method. The plasmid pGPU6 combined with cationic PEG-liposomes or Liopofectamin 2000 was used to transfect PC3 cells to judge the transfection efficiency. HE staining showed that the pGUP6-shAurora B plasmid/liposomes complex could significantly inhibit tumor growth in mice tumor model. The results indicated that there was no remarkable difference between the homemade liposomes and Lipofectamin 2000 after transfection, with transfection efficiency over 80%. And the homemade liposomes also had high transfection efficiency in vivo. No significant side effects were observed on weight, coat condition, behavior or appetite and the life span of mice treated with pGPU6-shAurora B were extended. Beyond that, there were no differences in mortality or in pathological changes to the heart, liver, spleen, lungs and kidneys among all the mice.

Topics: Animals; Aurora Kinase B; Cations; Cell Line, Tumor; Drug Delivery Systems; Fatty Acids, Monounsaturated; Female; Humans; Liposomes; Male; Mice, Inbred BALB C; Particle Size; Phosphatidylethanolamines; Polyethylene Glycols; Prostatic Neoplasms; Quaternary Ammonium Compounds; RNA, Small Interfering; Transfection; Xenograft Model Antitumor Assays

Application of superparamagnetic iron oxide nanoparticles (SPIOs) as the contrast agent has improved the quality of magnetic resonance (MR) imaging. Low efficiency of loading the commercially available iron oxide nanoparticles into cells and the cytotoxicity of previously formulated complexes limit their usage as the image probe. Here, we formulated new cationic lipid nanoparticles containing SPIOs feasible for in vivo imaging.. Hydrophobic SPIOs were incorporated into cationic lipid 1,2-dioleoyl-3-(trimethylammonium) propane (DOTAP) and polyethylene-glycol-2000-1,2-distearyl-3-sn-phosphatidylethanolamine (PEG-DSPE) based micelles by self-assembly procedure to form lipid-coated SPIOs (L-SPIOs). Trace amount of Rhodamine-dioleoyl-phosphatidylethanolamine (Rhodamine-DOPE) was added as a fluorescent indicator. Particle size and zeta potential of L-SPIOs were determined by Dynamic Light Scattering (DLS) and Laser Doppler Velocimetry (LDV), respectively. HeLa, PC-3 and Neuro-2a cells were tested for loading efficiency and cytotoxicity of L-SPIOs using fluorescent microscopy, Prussian blue staining and flow cytometry. L-SPIO-loaded CT-26 cells were tested for in vivo MR imaging.. The novel formulation generates L-SPIOs particle with the average size of 46 nm. We showed efficient cellular uptake of these L-SPIOs with cationic surface charge into HeLa, PC-3 and Neuro-2a cells. The L-SPIO-loaded cells exhibited similar growth potential as compared to unloaded cells, and could be sorted by a magnet stand over ten-day duration. Furthermore, when SPIO-loaded CT-26 tumor cells were injected into Balb/c mice, the growth status of these tumor cells could be monitored using optical and MR images.. We have developed a novel cationic lipid-based nanoparticle of SPIOs with high loading efficiency, low cytotoxicity and long-term imaging signals. The results suggested these newly formulated non-toxic lipid-coated magnetic nanoparticles as a versatile image probe for cell tracking.

Topics: Adenocarcinoma; Animals; Cations; Cell Differentiation; Cell Line, Tumor; Colorectal Neoplasms; Contrast Media; Fatty Acids, Monounsaturated; Feasibility Studies; Ferric Compounds; HeLa Cells; Humans; Hydrophobic and Hydrophilic Interactions; Magnetic Resonance Imaging; Male; Metal Nanoparticles; Mice; Mice, Inbred BALB C; Micelles; Neuroblastoma; Particle Size; Phosphatidylethanolamines; Polyethylene Glycols; Prostatic Neoplasms; Quaternary Ammonium Compounds; Rhodamines