Preparation, Characterization, and In Vitro pH-sensitivity Evaluation of Superparamagnetic Iron Oxide Nanoparticle- Misonidazole pH-sensitive Liposomes

2019 ◽  
Vol 16 (3) ◽  
pp. 254-267 ◽  
Author(s):  
Bibo Li ◽  
Biqiang Li ◽  
Daiying He ◽  
Changyan Feng ◽  
Zhibin Luo ◽  
...  

Background: The use of Misonidazole (MISO), the first and a potential hypoxic tumor cell radiosensitizer, has been limited by peripheral neurotoxicity, thus discouraging phase III clinical trials. Objective: To develop a targeted drug delivery and tracing System with pH-sensitive liposomes (SpHLs) and Superparamagnetic Iron Oxide Nanoparticles (SPIONs) to counter MISO-related adverse effects and to enable tracing under magnetic resonance. Methods: SPION-MISO-SpHLs were prepared by a reverse evaporation and freeze-thawing method. HPLC and phenanthroline spectrophotometry were established for MISO and Fe determination. The characterization and in vitro pH-sensitivity of SPION-MISO-SpHLs were evaluated. Results: The maximal entrapment efficiencies of MISO and SPIONs in SPION-MISO-SpHLs were 30.2% and 23.7%, respectively. The cumulative release rates of MISO and SPIONs were respectively 2.49 and 2.47 times higher in pH 5.5 than in pH 7.4 buffer. The mean particle size of SPION-MISOSpHLs was 950 nm. The zeta potential was -58.9 mV in pH 7.4 buffer and 36.3 mV in pH 5.5 buffer. SEM imaging showed that SPION-MISO-SpHLs had similar spherical morphologies. SPIONs were packed in the center of liposomes and were well dispersed in a TEM graph. Magnetization curve showed that SPION-MISO-SpHLs retained superparamagnetic properties. SPION-MISO-SpHLs were compared with MISO+SPION+blank liposome in hypoxia and control groups of A549 cells. MISO and SPION concentrations in culture medium showed significant differences between the same concentration groups (P < 0.0001) and at different times (P < 0.0001). Conclusion: SPION-MISO-SpHLs possess pH-dependent release ability and superparamagnetism, and thus provides a system for targeted delivery and tracing under magnetic resonance.

2008 ◽  
Vol 108 (2) ◽  
pp. 320-329 ◽  
Author(s):  
Xing Wu ◽  
Jin Hu ◽  
Liangfu Zhou ◽  
Ying Mao ◽  
Bojie Yang ◽  
...  

Object Mesenchymal stem cells (MSCs) have been shown to migrate toward tumors, but their distribution pattern in gliomas has not been completely portrayed. The primary purpose of the study was to assay the tropism capacity of MSCs to gliomas, to delineate the pattern of MSC distribution in gliomas after systemic injection, and to track the migration and incorporation of magnetically labeled MSCs using 1.5-T magnetic resonance (MR) imaging. Methods The MSCs from Fischer 344 rats were colabeled with superparamagnetic iron oxide nanoparticles (SPIO) and enhanced green fluorescent protein (EGFP). The tropism capacity of MSCs was quantitatively assayed in vitro using the Transwell system. To track the migration of MSCs in vivo, MR imaging was performed both 7 and 14 days after systemic administration of labeled MSCs. After MR imaging, the distribution patterns of MSCs in rats with gliomas were examined using Prussian blue and fluorescence staining. Results The in vitro study showed that MSCs possessed significantly greater migratory capacity than fibroblast cells (p < 0.001) and that lysis of F98 glioma cells and cultured F98 cells showed a greater capacity to induce migration of cells than other stimuli (p < 0.05). Seven days after MSC transplantation, the SPIO–EGFP colabeled cells were distributed throughout the tumor, where a well-defined dark hypointense region was represented on gradient echo sequences. After 14 days, most of the colabeled MSCs were found at the border between the tumor and normal parenchyma, which was represented on gradient echo sequences as diluted amorphous dark areas at the edge of the tumors. Conclusions This study demonstrated that systemically transplanted MSCs migrate toward gliomas with high specificity in a temporal–spatial pattern, which can be tracked using MR imaging.


2008 ◽  
Vol 94 (2) ◽  
pp. 226-233 ◽  
Author(s):  
Carlo Emanuele Neumaier ◽  
Gabriella Baio ◽  
Silvano Ferrini ◽  
Giorgio Corte ◽  
Antonio Daga

Ultrasmall superparamagnetic iron oxide nanoparticles and magnetic resonance imaging provide a non-invasive method to detect and label tumor cells. These nanoparticles exhibit unique properties of superparamagnetism and can be utilized as excellent probes for magnetic resonance imaging. Most work has been performed using a magnetic resonance scanner with high field strength up to 7 T. Ultrasmall superparamagnetic iron oxide nanoparticles may represent a suitable tool for labeling molecular probes that target specific tumor-associated markers for in vitro and in vivo detection by magnetic resonance imaging. In our study, we demonstrated that magnetic resonance imaging at 1.5 T allows the detection of ultrasmall superparamagnetic iron oxide nanoparticle conjugated antibody specifically bound to human tumor cells in vitro and in vivo, and that the magnetic resonance signal intensity correlates with the concentration of ultrasmall superparamagnetic iron oxide nanoparticle antibody used and with the antigen density at the cell surface. The experiments were performed using two different means of targeting: direct and indirect magnetic tumor targeting. The imaging of tumor antigens using immunospecific contrast agents is a rapidly evolving field, which can potentially aid in early disease detection, monitoring of treatment efficacy, and drug development. Cell labeling by iron oxide nanoparticles has emerged as a potentially powerful tool to monitor trafficking of a large number of cells in the cell therapy field. We also studied the labeling of natural killer cells with iron nanoparticles to a level that would allow the detection of their signal intensity with a clinical magnetic resonance scanner at 1.5 T. Magnetic resonance imaging and iron magnetic nanoparticles are able to increase the accuracy and the specificity of imaging and represent new imaging opportunities in preclinical and translational research.


2018 ◽  
Vol 315 (3) ◽  
pp. 595-602 ◽  
Author(s):  
Esra Korkmaz Kirakli ◽  
Gökhan Takan ◽  
Sinan Hoca ◽  
F. Zümrüt Biber Müftüler ◽  
Ayfer Yurt Kılçar ◽  
...  

Pharmaceutics ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 120 ◽  
Author(s):  
Thai Hoang Thi ◽  
Diem-Huong Nguyen Tran ◽  
Long Bach ◽  
Hieu Vu-Quang ◽  
Duy Nguyen ◽  
...  

Polymer coating has drawn increasing attention as a leading strategy to overcome the drawbacks of superparamagnetic iron oxide nanoparticles (SPIONs) in targeted delivery of anticancer drugs. In this study, SPIONs were modified with heparin-Poloxamer (HP) shell to form a SPION@HP core-shell system for anticancer drug delivery. The obtained formulation was characterized by techniques including transmission electron microscopy (TEM), Fourier transform infrared spectra (FT-IR), vibration sample magnetometer (VSM), proton nuclear magnetic resonance (1H-NMR), and powder X-ray diffraction (XRD). Results showed the successful attachment of HP shell on the surface of SPION core and the inability to cause considerable effects to the crystal structure and unique magnetic nature of SPION. The core-shell system maintains the morphological features of SPIONs and the desired size range. Notably, Doxorubicin (DOX), an anticancer drug, was effectively entrapped into the polymeric shell of SPION@HP, showing a loading efficiency of 66.9 ± 2.7% and controlled release up to 120 h without any initial burst effect. Additionally, MTT assay revealed that DOX-loaded SPION@HP exerted great anticancer effect against HeLa cells and could be safely used. These results pave the way for the application of SPION@HP as an effective targeted delivery system for cancer treatment.


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