dioleoyl-phosphatidylethanolamine and Adenocarcinoma

To develop a photosensitizer, chlorin e6 (Ce6)-based amphiphilic polymer, DP-Ce6, where DOPE and PEG are conjugated to Ce6, which would self-assemble to form polymeric micelles (DP-Ce6-M) in aqueous environment.. DP-Ce6-M were characterized for particle size, zeta potential, and singlet oxygen (. DP-Ce6-M formed stable micelles with particles size of 58.2 ± 1.6 nm. Solubility of Ce6 was improved. Photoactivity of DP-Ce6-M was sustained in regard to

Topics: Adenocarcinoma; Cell Line, Tumor; Chlorophyllides; Female; Humans; Lipids; Micelles; Nanoparticles; Particle Size; Phosphatidylethanolamines; Photochemotherapy; Photosensitizing Agents; Polyethylene Glycols; Polymers; Porphyrins; Uterine Neoplasms

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

Three cationic cholesterol derivatives (CCDs), which differ in their types of amine and bear a hydroxyethyl group at the amine group, were synthesized and formulated into liposomes and nanoparticles as gene delivery vectors. In vitro transfection into A549 cells proved that liposomes formulated with CCDs and dioleoylphosphatidylethanolamine (DOPE) of 1/2 molar ratio were more effective than the corresponding nanoparticles with CCDs and Tween 80 at charge ratios (+/-) of 1/2, 3/1 and 5/1. Among the liposomal formulations, non-hydroxyethylated CCDs were more effective than hydroxyethylated ones in vitro. However, gene transfection in the lung through intratracheal injection showed opposite results to those in vitro, with liposomes containing hydroxyethylated CCDs being more potent than those containing non-hydroxyethylated CCDs. Transfection by liposomes with N,N-methyl hydroxyethyl aminopropane carbamoyl cholesterol iodide (MHAPC) showed the highest luciferase activity, resulting in 2- and 60-fold higher gene expression than jet-PEI and naked DNA, respectively. The distribution of MHAPC lipoplex after intratracheal injection was heterogeneous, and luciferase was expressed in epithelial cells lining the bronchi and bronchioles. All the lipoplexes led to higher TNF-alpha levels in the lung compared to the nanoplex and jet-PEI, but our findings suggested that modification of the cationic cholesterol with a hydroxyethyl group at the tertiary amine terminal, MHAPC, promoted gene expression in the lung without increasing the toxicity compared with other CCDs. This work firstly proved that liposomes containing hydroxyethylated CCDs could promote gene expression in the lung through intratracheal injection.

Topics: Adenocarcinoma; Animals; Cations; Cell Line, Tumor; Cholesterol; Gene Expression Regulation; Genetic Vectors; Humans; Liposomes; Luciferases; Lung; Lung Neoplasms; Mice; Nanoparticles; Phosphatidylethanolamines; Structure-Activity Relationship; Tissue Distribution; Transfection