Dual Labeling of Primary Cells with Fluorescent Gadolinium Oxide Nanoparticles.

The interest in mesenchymal stromal cells as a therapy option is increasing rapidly. To improve their implementation, location, and distribution, the properties of these must be investigated. Therefore, cells can be labeled with nanoparticles as a dual contrast agent for fluorescence and magnetic resonance imaging (MRI). In this study, a more efficient protocol for an easy synthesis of rose bengal-dextran-coated gadolinium oxide (Gd2O3-dex-RB) nanoparticles within only 4 h was established. Nanoparticles were characterized by zeta potential measurements, photometric measurements, fluorescence and transmission electron microscopy, and MRI. In vitro cell experiments with SK-MEL-28 and primary adipose-derived mesenchymal stromal cells (ASC), nanoparticle internalization, fluorescence and MRI properties, and cell proliferation were performed. The synthesis of Gd2O3-dex-RB nanoparticles was successful, and they were proven to show adequate signaling in fluorescence microscopy and MRI. Nanoparticles were internalized into SK-MEL-28 and ASC via endocytosis. Labeled cells showed sufficient fluorescence and MRI signal. Labeling concentrations of up to 4 mM and 8 mM for ASC and SK-MEL-28, respectively, did not interfere with cell viability and proliferation. Gd2O3-dex-RB nanoparticles are a feasible contrast agent to track cells via fluorescence microscopy and MRI. Fluorescence microscopy is a suitable method to track cells in in vitro experiments with smaller samples.

Magnetic Fluid Hyperthermia as Treatment Option for Pancreatic Cancer Cells and Pancreatic Cancer Organoids.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) is a cancer with a meager prognosis due to its chemotherapy resistance. A new treatment method may be magnetic fluid hyperthermia (MFH). Magnetoliposomes (ML), consisting of superparamagnetic iron oxide nanoparticles (SPION) stabilized with a phospholipid-bilayer, are exposed to an alternating magnetic field (AMF) to generate heat. To optimize this therapy, we investigated the effects of MFH on human PDAC cell lines and 3D organoid cultures. MATERIAL AND METHODS: ML cytotoxicity was tested on Mia PaCa-2 and PANC-1 cells and on PDAC 3D organoid cultures, generated from resected tissue of patients. The MFH was achieved by AMF application with an amplitude of 40-47 kA/m and a frequency of 270 kHz. The MFH effect on the cell viability of the cell lines and the organoid cultures was investigated at two different time points. Clonogenic assays evaluated the impairment of colony formation. Altering ML set-ups addressed differences arising from intra- vs extracellular ML locations. RESULTS: Mia PaCa-2 and PANC-1 cells showed no cytotoxic effects at ML concentrations up to 300 µg(Fe)/mL and 225 µg(Fe)/mL, respectively. ML at a concentration of 225 µg(Fe)/mL were also non-toxic for PDAC organoid cultures. MFH treatment using exclusively extracellular ML presented the highest impact on cell viability. Clonogenic assays demonstrated remarkable impairment as long-term outcome in MFH-treated PDAC cell lines. Additionally, we successfully treated PDAC organoids with extracellular ML-derived MFH, resulting in notably reduced cell viabilities 2h and 24 h post treatment. Still, PDAC organoids seem to partly recover from MFH after 24 h as opposed to conventional 2D-cultures. CONCLUSION: Treatment with MFH strongly diminished pancreatic cancer cell viability in vitro, making it a promising treatment strategy. As organoids resemble the more advanced in vivo conditions better than conventional 2D cell lines, our organoid model holds great potential for further investigations.

Nanomagnetic Actuation of Hybrid Stents for Hyperthermia Treatment of Hollow Organ Tumors.

This paper describes a magnetic nanotechnology that locally enables hyperthermia treatment of hollow organ tumors by using polymer hybrid stents with incorporated magnetic nanoparticles (MNP). The hybrid stents are implanted and activated in an alternating magnetic field to generate therapeutically effective heat, thereby destroying the tumor. Here, we demonstrate the feasibility of nanomagnetic actuation of three prototype hybrid stents for hyperthermia treatment of hollow organ tumors. The results show that the heating efficiency of stent filaments increases with frequency from approximately 60 W/gFe (95 kHz) to approximately 250 W/gFe (270 kHz). The same trend is observed for the variation of magnetic field amplitude; however, heating efficiency saturates at approximately 30 kA/m. MNP immobilization strongly influences heating efficiency showing a relative difference in heating output of up to 60% compared to that of freely dispersed MNP. The stents showed uniformly distributed heat on their surface reaching therapeutically effective temperatures of 43 °C and were tested in an explanted pig bile duct for their biological safety. Nanomagnetic actuation of hybrid stents opens new possibilities in cancer treatment of hollow organ tumors.

Size-Tailored Biocompatible FePt Nanoparticles for Dual T1/T2 Magnetic Resonance Imaging Contrast Enhancement.

The development of new contrast agents (CAs) for magnetic resonance imaging (MRI) is of high interest, especially because of the increased concerns of patient safety and quick clearance of clinically used gadolinium and iron oxide-based CAs, respectively. Here, a two-step synthesis of superparamagnetic water-soluble iron platinum (FePt) nanoparticles (NPs) with core sizes between 2 and 8 nm for use as CAs in MRI is reported. First, wet-chemical organometallic NPs are synthesized by thermal decomposition in the presence of stabilizing oleic acid and oleylamine. Second, the hydrophobic NPs are coated with an amphiphilic polymer and transferred into aqueous media. Their magnetization values and relaxation rates exceed those published for CAs already used for clinical application. Their saturation magnetization increases with the core size to approximately 82 A·m2/kgFe. For 8 nm NPs, the T2 relaxivity of approximately 221 (mM·s)-1 is 5 times larger than that for the ferumoxides, and for 6 nm NPs, the T1 relaxivity of approximately 12 (mM·s)-1 is slightly higher than that of ultrasmall gadolinium oxide NPs. The 6 nm FePt NPs are identified as excellent CAs for both T1 and T2 imaging. Most importantly, because of their coating, significantly low cytotoxicity is achieved. FePt NPs prove to be a promising alternative to gadolinium and iron oxide NPs showing high-quality CA characteristics for both T1- and T2-weighted images.