Gadolinium (Gd) contrast agents are predominantly used for T1 MR imaging. However, the high toxicity of Gd3+ and potential side effects including nephrogenic systemic fibrosis have led to the search for alternative T1 contrast agents. Since manganese (Mn) has paramagnetic properties with five unpaired electrons that permit high spin number, long electronic relaxation times, and labile water exchange, we evaluated Mn as a T1 magnetic resonance imaging (MRI) contrast agent for lung imaging. Here we report on the design and synthesis of multifunctional lipid-micellar nanoparticles (LMNs) containing Mn oxide (M-LMNs) for MRI that can also be used for DNA and drug delivery. Oleic acid-coated MnO nanoparticles were encapsulated in micelles composed of polyethylene glycol (PEG-2000), phosphatidylethanolamine (PE), DC-cholesterol, and dioleoyl-phosphatidylethanolamine (DOPE). The particles are taken up in vitro by human embryonic kidney (HEK293), Lewis lung carcinoma (LLC1), and A549 cells and are devoid of cytotoxicity. When administered to mice intranasally, they preferentially accumulate in the lungs. In vitro phantom and ex vivo lung MRI results confirmed that M-LMNs are able to enhance T1 MRI contrast. M-LMNs loaded with plasmid DNA and/or doxorubicin are efficiently taken up by HEK293 cells in vitro and by target cells in vivo. Taken together, these results demonstrate that M-LMNs are capable of simultaneously providing MRI contrast and DNA and/or drug delivery to target cells in the lung and therefore may prove useful as a lung theranostic, especially for lung cancers.
Improving the sensitivity of existing biosensors for highly sensitive detection of magnetic nanoparticles as biomarkers in biological systems is an important and challenging task. Here, we propose a method of combining the magneto-resistance (MR), magneto-reactance (MX), and magneto-impedance (MI) effects to develop an integrated magnetic biosensor with tunable and enhanced sensitivity. A systematic study of the 7 nm Fe 3 O 4 nanoparticle concentration dependence of MR, MX, and MI ratios of a soft ferromagnetic amorphous ribbon shows that these ratios first increase sharply with increase in particle concentration (0-124 nM) and then remain almost unchanged for higher concentrations (124 nM-1240 nM). The MX-based biosensor shows the highest sensitivity. With this biosensor, $2.1 Â 10 11 7 nm Fe 3 O 4 nanoparticles can be detected over a detection area of 2.0 Â 10 5 lm 2 , which is comparable to a superconducting quantum interference device biosensor that detects the presence of $1 Â 10 8 11 nm Fe 3 O 4 nanoparticles over a detection area of 6.8 Â 10 4 lm 2. The proposed biosensor can detect low and various concentrations of superparamagnetic nanoparticles (below 10 nm in size), which is of practical importance in biosensing applications. V
Theranostic nanoparticles with both therapeutic and imaging abilities have the promise to revolutionize diagnosis, therapy, and prognosis. Early and accurate detection along with swift treatment are the most important steps in the successful treatment of any disease. Over the last decade, a variety of nanotechnology-based platforms have been created in the hope of improving the treatment and diagnosis of a wide variety of diseases. However, significant hurdles still remain before theranostic nanoparticles can bring clinical solutions to the fight against chronic respiratory diseases. Some fundamental issues such as long-term toxicity, a precise understanding of the accumulation, degradation and clearance of these particles, and the correlation between basic physicochemical properties of these nanoparticles and their in vivo behavior have to be fully understood before they can be used clinically. To date, very little theranostic nanoparticle research has focused on the treatment and diagnosis of chronic respiratory illnesses. Nanomedicine approaches incorporating these theranostic nanoparticles could potentially be translated into clinical advances to improve diagnosis and treatment of these chronic respiratory diseases and enhance quality of life for the patients.
Diquat herbicide and rhodamine WT dye were applied in a lake to three 1.6 ha plots either with a polymer, which reportedly aids in sinking and confinement of aquatic herbicides, or without a polymer. Diquat and dye concentrations were measured at three different depths in the water column within the plots during the first three hours after application to determine vertical distribution of diquat and dye, and in composite samples at fixed distances from the plot up to 168 hours after application to determine movement out of the treated plots. Diquat and dye were homogeneous in the water column when no polymer was used, but were concentrated near the surface when polymer was used. This distribution may have resulted from temperature stratification. Polymer did not affect movement of diquat or dye out of the plots. The half‐lives of diquat within the plots were 25 (SE=6.2) hr, 39 (SE=4.3) hr, and 25 (SE=2.0) hr. Forty‐six percent of samples collected at the edges of the plots did not contain detectable diquat residues and only 66 percent of those samples with detectable diquat contained greater than the potable water tolerance (10 ppb). Diquat was not found in any samples 168 hours after application 61 m or farther from the edge of the plots. Dye and diquat concentrations were weakly correlated within and outside the plots. Dye half‐lives were consistently higher than diquat, which suggests that the herbicide was removed from the water by plants and sediments more rapidly than dye.
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