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1.  Biodistribution, kinetics, and biological fate of SPION microbubbles in the rat 
Background
In the present investigation, we studied the kinetics and biodistribution of a contrast agent consisting of poly(vinyl alcohol) (PVA) microbubbles containing superparamagnetic iron oxide (SPION) trapped between the PVA layers (SPION microbubbles).
Methods
The biological fate of SPION microbubbles was determined in Sprague-Dawley rats after intravenous administration. Biodistribution and elimination of the microbubbles were studied in rats using magnetic resonance imaging for a period of 6 weeks. The rats were sacrificed and perfusion-fixated at different time points. The magnetic resonance imaging results obtained were compared with histopathologic findings in different organs.
Results
SPION microbubbles could be detected in the liver using magnetic resonance imaging as early as 10 minutes post injection. The maximum signal was detected between 24 hours and one week post injection. Histopathology showed the presence of clustered SPION microbubbles predominantly in the lungs from the first time point investigated (10 minutes). The frequency of microbubbles declined in the pulmonary vasculature and increased in pulmonary, hepatic, and splenic macrophages over time, resulting in a relative shift from the lungs to the spleen and liver. Meanwhile, macrophages showed increasing signs of cytoplasmic iron accumulation, initially in the lungs, then followed by other organs.
Conclusion
The present investigation highlights the biological behavior of SPION microbubbles, including organ distribution over time and indications for biodegradation. The present results are essential for developing SPION microbubbles as a potential contrast agent and/or a drug delivery vehicle for specific organs. Such a vehicle will facilitate the use of multimodality imaging techniques, including ultrasound, magnetic resonance imaging, and single positron emission computed tomography, and hence improve diagnostics, therapy, and the ability to monitor the efficacy of treatment.
doi:10.2147/IJN.S49948
PMCID: PMC3767493  PMID: 24023513
biodistribution; microbubbles; superparamagnetic iron oxide; pharmacokinetics; magnetic resonance imaging; histopathology
2.  Nanocomposites of polymer and inorganic nanoparticles for optical and magnetic applications 
Nano Reviews  2010;1:10.3402/nano.v1i0.5214.
This article provides an up-to-date review on nanocomposites composed of inorganic nanoparticles and the polymer matrix for optical and magnetic applications. Optical or magnetic characteristics can change upon the decrease of particle sizes to very small dimensions, which are, in general, of major interest in the area of nanocomposite materials. The use of inorganic nanoparticles into the polymer matrix can provide high-performance novel materials that find applications in many industrial fields. With this respect, frequently considered features are optical properties such as light absorption (UV and color), and the extent of light scattering or, in the case of metal particles, photoluminescence, dichroism, and so on, and magnetic properties such as superparamagnetism, electromagnetic wave absorption, and electromagnetic interference shielding. A general introduction, definition, and historical development of polymer–inorganic nanocomposites as well as a comprehensive review of synthetic techniques for polymer–inorganic nanocomposites will be given. Future possibilities for the development of nanocomposites for optical and magnetic applications are also introduced. It is expected that the use of new functional inorganic nano-fillers will lead to new polymer–inorganic nanocomposites with unique combinations of material properties. By careful selection of synthetic techniques and understanding/exploiting the unique physics of the polymeric nanocomposites in such materials, novel functional polymer–inorganic nanocomposites can be designed and fabricated for new interesting applications such as optoelectronic and magneto-optic applications.
doi:10.3402/nano.v1i0.5214
PMCID: PMC3215211  PMID: 22110855
nano-filler; nano-inclusion; hybrid; effective additive; surface modification; superparamagnetism; UV absorption; in-situ polymerization; dichroism
3.  Iron oxide-based nanomagnets in nanomedicine: fabrication and applications 
Nano Reviews  2010;1:10.3402/nano.v1i0.4883.
Iron oxide-based nanomagnets have attracted a great deal of attention in nanomedicine over the past decade. Down to the nanoscale, superparamagnetic iron oxide nanoparticles can only be magnetized in the presence of an external magnetic field, which makes them capable of forming stable colloids in a physio-biological medium. Their superparamagnetic property, together with other intrinsic properties, such as low cytotoxicity, colloidal stability, and bioactive molecule conjugation capability, makes such nanomagnets ideal in both in-vitro and in-vivo biomedical applications. In this review, a chemical, physical, and biological synthetic approach to prepare iron oxide-based nanomagnets with different physicochemical properties was illustrated and compared. The growing interest in iron oxide-based nanomagnets with multifunctionalities was explored in cancer diagnostics and treatment, focusing on their combined roles in a magnetic resonance contrast agent, hyperthermia, and magnetic force assisted drug delivery. Iron oxides as magnetic carriers in gene therapy were reviewed with a focus on the sophisticated design and construction of magnetic vectors. Finally, the iron oxide-based nanomagnet also represents a very promising tool in particle/cell interfacing in controlling cellular functionalities, such as adhesion, proliferation, differentiation, and cell patterning, in stem cell therapy and tissue engineering applications.
doi:10.3402/nano.v1i0.4883
PMCID: PMC3215210  PMID: 22110854
iron oxide; coprecipitation; thermal decomposition; microemulsion; magnetosome; lithography; cancer targeting; stem cell; gene delivery; tissue engineering; cell actuation
4.  Microsomal Glutathione Transferase 1 Protects Against Toxicity Induced by Silica Nanoparticles but Not by Zinc Oxide Nanoparticles 
ACS Nano  2012;6(3):1925-1938.
Microsomal glutathione transferase 1 (MGST1) is an antioxidant enzyme located predominantly in the mitochondrial outer membrane and endoplasmic reticulum and has been shown to protect cells from lipid peroxidation induced by a variety of cytostatic drugs and pro-oxidant stimuli. We hypothesized that MGST1 may also protect against nanomaterial-induced cytotoxicity through a specific effect on lipid peroxidation. We evaluated the induction of cytotoxicity and oxidative stress by TiO2, CeO2, SiO2, and ZnO in the human MCF-7 cell line with or without overexpression of MGST1. SiO2 and ZnO nanoparticles caused dose- and time-dependent toxicity, whereas no obvious cytotoxic effects were induced by nanoparticles of TiO2 and CeO2. We also noted pronounced cytotoxicity for three out of four additional SiO2 nanoparticles tested. Overexpression of MGST1 reversed the cytotoxicity of the main SiO2 nanoparticles tested and for one of the supplementary SiO2 nanoparticles but did not protect cells against ZnO-induced cytotoxic effects. The data point toward a role of lipid peroxidation in SiO2 nanoparticle-induced cell death. For ZnO nanoparticles, rapid dissolution was observed, and the subsequent interaction of Zn2+ with cellular targets is likely to contribute to the cytotoxic effects. A direct inhibition of MGST1 by Zn2+ could provide a possible explanation for the lack of protection against ZnO nanoparticles in this model. Our data also showed that SiO2 nanoparticle-induced cytotoxicity is mitigated in the presence of serum, potentially through masking of reactive surface groups by serum proteins, whereas ZnO nanoparticles were cytotoxic both in the presence and in the absence of serum.
doi:10.1021/nn2021056
PMCID: PMC3314313  PMID: 22303956
engineered nanoparticles; oxidative stress; lipid peroxidation; microsomal glutathione transferase 1

Results 1-4 (4)