Open Access

Hyperthermia with the use of magnetic nanoparticles (MNP) is a challenging but most promising approach for cancer therapy. After being magnetically trapped at the tumor site, MNP are heated in alternating magnetic fields (AMF) to approx. 43 °C, which causes tumor cell apoptosis. For an effective and controllable hyperthermia application, two parameters are most important: the amount of internalized MNP in tumor cells and their heating characteristics in AMF. In this study, we evaluated if a sufficient temperature could be achieved by cell internalized MNP heated up in AMF and if cell death could be induced in this way. The heating of pancreatic tumor cell lines MiaPaCa-2 and BxPC-3 loaded with different amounts of selfsynthesized magnetoliposomes nanoparticles (MLs) was measured with a custom-built setup. The MLs consisted of a fluorescent bi-layer of phospholipids and multiple magnetite (Fe3O4) cores with a diameter of (10.0 ± 0.5) nm each. The hydrodynamic diameter of the MLs was (90 ± 5) nm. Cell loading was performed by incubation of tumor cells for up to 24 h at 37 °C in a DMEM cell medium with MLs, which had an iron concentration of 150 μg/mL. Transmission electron microscopy and fluorescence microscopy were used to depict the uptake of MLs into the tumor cells (see Figure). The internalized iron-content per cell was determined with a magnetic particle spectrometer (MPS). After application of AMF for approx. 30 min, cell viability was assessed by clonogenic assay. The cellular uptake of MLs was time-dependent, cell line-specific and saturated: For both MiaPaCa-2 and BxPC-3 cell lines, the MLs cell internalization followed an exponential growth function which saturated after about 24 h cell incubation time at an iron load of (110 ± 6) pg/cell and (30 ± 2) pg/cell, respectively. The time constants of the exponential growth were (7.2 ± 1.4) h and (4.0 ± 0.6) h, respectively. In AMF, cells with the saturated MLs loading reached temperatures of approx. 44 °C and 43.5 °C, which caused the cell survival fraction to drop to approx. one third compared to untreated tumor cells for both MiaPaCa-2 and BxPC-3 cell lines. These results demonstrate the feasibility of hyperthermia in pancreatic cancer treatment by confirming cell death of pancreatic tumor cells at temperatures of approx. 43 °C. Further investigations are planned, which aim for the optimization of MNP dosage in targeting experiments as well as the assessment of incubation times and AMF parameters needed for a successful hyperthermic therapy.

Purpose: It was demonstrated previously that retinal pulse wave velocity (rPWV) as a measure of retinal arterial stiffness is increased in aged anamnestically healthy volunteers compared with young healthy subjects. Using novel methodology of rPWV assessment this finding was confirmed and investigated whether it might relate to the increased blood pressure usually accompanying the aging process, rather than to the aging itself. Methods: A total of 12 young 25.5-year-old (24.0–28.8) [median(1st quartile–3rd quartile)] and 12 senior 68.5-year-old (63.8–71.8) anamnestically healthy volunteers; and 12 senior 63.0-year-old (60.8–65.0) validated healthy volunteers and 12 young 33.0-year-old (29.5–35.0) hypertensive patients were examined. Time-dependent alterations of vessel diameter were assessed by the Dynamic Vessel Analyzer in a retinal artery of each subject. The data were filtered and processed using mathematical signal analysis and rPWVs were calculated. Results: rPWV amounted to 1200 (990-1470) RU (relative units)/s in the hypertensive group and to 1040 (700-2230) RU/s in anamnestically healthy seniors. These differed significantly from rPWVs in young healthy group (410 [280–500] RU/s) and in validated healthy seniors (400 [320–510] RU/s). rPWV associated with age and mean arterial pressure (MAP) in the pooled cohort excluded validated healthy seniors. In a regression model these associations remain when alternately adjusted for MAP and age. When including validated healthy seniors in the pooled cohort only association with MAP remains. Conclusions: Both aging (with not excluded cardiovascular risk factors) and mild hypertension are associated with elevated rPWV. rPWV increases to a similar extent both in young mildly hypertensive subjects and in aged anamnestically healthy persons. Healthy aging is not associated with increased rPWV.