Roland Jurgons

Targeting cancer cells: magnetic nanoparticles as drug carriers

Magnetic drug targeting employing nanoparticles as carriers is a promising cancer treatment avoiding side effects of conventional chemotherapy. We used iron oxide nanoparticles covered by starch derivatives with phosphate groups which bound mitoxantrone as chemotherapeutikum. In this letter we show that a strong magnetic field gradient at the tumour location accumulates the nanoparticles. Electron microscope investigations show that the ferrofluids can be enriched in tumour tissue and tumour cells.

Drug loaded magnetic nanoparticles for cancer therapy

Magnetic nanoparticles have been investigated for biomedical applications for more than 30 years. In medicine they are used for several approaches such as magnetic cell separation or magnetic resonance imaging (MRI). The development of biocompatible nanosized drug delivery systems for specific targeting of therapeutics is the focus of medical research, especially for the treatment of cancer and diseases of the vascular system. In an experimental cancer model, we performed targeted drug delivery and used magnetic iron oxide nanoparticles, bound to a chemotherapeutic agent, which were attracted to an experimental tumour in rabbits by an external magnetic field (magnetic drug targeting). Complete tumour remission could be achieved. An important advantage of these carriers is the possibility for detecting these nanoparticles after treatment with common imaging techniques (i.e. x-ray-tomography, magnetorelaxometry, magnetic resonance imaging), which can be correlated to histology.

Design and Evaluation of Magnetic Fields for Nanoparticle Drug Targeting in Cancer

The retention of superparamagnetic nanoparticles under the influence of a high-gradient magnetic field was investigated. A simulation algorithm for prediction of the particles trajectories and, therefore, the total amount of adhered particles in an artificial vessel was developed. Comparisons between in vitro experiments and simulations showed that the required experimental magnetic moments were greater than the theoretically estimated magnetic moments. This paper presents a method for investigating magnetic fields and for determining the magnetic moment of particles by simulation of their trajectories. The detailed function of magnetic drug targeting is of great importance in animal studies and in human therapies

Determination of the magnetic particle distribution in tumour tissue by means of x-ray tomography

In biomedical applications of ferrofluids, the resulting distribution of the magnetic nanoparticles is a crucial parameter for the effect of the therapeutic approach. In order to increase the efficacy of local cancer treatments incorporating ferrofluids like magnetic drug targeting and hyperthermia, the bio-distribution of theses fluids in the respective tissue has to be optimized. Usually, the distribution of particles is determined by histological cuts of the investigated specimen, a technique which provides only local information about the overall distribution of the magnetic material, e.g.?in a tumour. Radioscopic techniques based on gamma or x-rays are well established, suitable for in?vivo examination and non-destructive, but only provide two-dimensional integral information in the direction of the beam. Here we have used micro-tomography?incorporating a conventional x-ray tube as well as monochromatic synchrotron radiation?as a tool for a three-dimensional analysis of the distribution of magnetic nanoparticles in biological applications. Compared to biological matter, the iron-based magnetic nanoparticles provide sufficiently high absorption for x-rays and thus serve as an intrinsic contrast agent for the examinations. The results show the principle feasibility of the method for a quantitative determination of the agglomeration behaviour of the nanoparticles within carcinogenic tissue after intravascular or intratumoural injection.

Targeted Tumor Therapy with “Magnetic Drug Targeting”: Therapeutic Efficacy of Ferrofluid Bound Mitoxantrone

The difference between success or failure of chemotherapy depends not only on the drug itself but also on how it is delivered to its target. Biocompatible ferrofluids (FF) are paramagnetic nanoparticles, that may be used as a delivery system for anticancer agents in locoregional tumor therapy, called “magnetic drug targeting”. Bound to medical drugs, such magnetic nanoparticles can be enriched in a desired body compartment (tumor) using an external magnetic field, which is focused on the area of the tumor. Through this form of target directed drug application, one attempts to concentrate a pharmacological agent at its site of action in order to minimize unwanted side effects in the organism and to increase its locoregional effectiveness.

Does stimulation with human gonadotropins and gonadotropin-releasing hormone agonist enhance and accelerate the developmental capacity of oocytes in human ovarian tissue xenografted into severe combined immunodeficient mice?

OBJECTIVE To assess the capacity of human frozen-thawed ovarian follicles matured in xenografts to form metaphase II (MII) oocytes after xenotransplantation and exogenous stimulation. DESIGN Prospective controlled animal study. SETTING University hospital gynecology research unit. PATIENT(S) Ovarian fragments were obtained from 17 women with malignant diseases who wished to cryopreserve ovarian tissue for later pregnancy before chemotherapy. ANIMAL(S) Eighty-eight female severe combined immunodeficient (SCID) mice. INTERVENTION(S) Cryopreserved human ovarian tissue was grafted into oophorectomized SCID mice. The mice were divided into three groups: Group A received hMG alone every 2 days for a maximum of 24 weeks; group B additionally received nRH agonist (GnRHa) every 4 weeks; and group C was an untreated control group. MAIN OUTCOME MEASURE(S) Follicular density, morphology, proliferation, oocyte maturation, malignant cell contamination. RESULT(S) Follicle survival and development were similar in all three groups. No significant interactions between the stimulation protocols and grafting duration were noted. Three MII oocytes were observed in grafted follicles. Two MII oocytes were harvested without stimulation. None of the mice showed signs of reintroduced malignancy, nor did microscopic evaluation of the grafts raise any suspicion of residual malignant disease. CONCLUSION(S) After xenotransplantation, human primordial follicles can be matured to MII oocytes even without stimulation. Administering human gonadotropin and GnRHa does not enhance the developmental capacity of xenografted oocytes. The optimal stimulation schedule for grafted tissue remains unknown.

Distribution of Mitoxantrone after Magnetic Drug Targeting: Fluorescence Microscopic Investigations on VX2 Squamous Cell Carcinoma Cells

Summary Magnetic drug targeting (MDT) is a new approach in local cancer therapy. Starch coated magnetite nanoparticles bound to the chemotherapeutic agent mitoxantrone can be enriched in the tumor region of a VX2 squamous cell carcinoma in rabbits. Using fluorescence-microscopy we showed enrichment of the chemotherapeutic agent in its site of action, the DNA.

Distribution of Magnetic Nanoparticles after Magnetic Drug Targeting in an ExVivo Bovine Artery Model

The aim of Magnetic Drug Targeting (MDT) in cancer therapy is to concentrate chemotherapeutics to a tumor region while simultaneously the over all dose is reduced. This can be achieved by coated superparamagnetic nanoparticles bound to a chemotherapeutic agent. These particles are applied intraarterially close to the tumor region and focused to the tumor by a strong external magnetic field. The interaction of the particles with the field should make them accumulate in the region of the steepest field gradient. Here, we suggest an artery model by which the magnetic targeting mechanism can be studied in detail. In particular, we focus on the quantification of the accumulation profile along the artery by SQUID-based magnetorelaxometry.

Diagnostic Imaging in Cancer Therapy with Magnetic Nanoparticles

The unfavorable application-to-tumor-dose-ratio is a drawback of conventional systemic chemotherapy, implying an often insufficient drug dose in the tumor being associated with severe side effects for the patient. The use of chemotherapeutics bound to magnetic nanoparticles offers several advantages. On the one hand it is possible to concentrate the chemotherapeutics in the tumor region by the use of magnetic fields, like it is done in Magnetic Drug Targeting (MDT). On the other hand magnetic particles can serve as contrast agent for magnetic resonance imaging (MRI) that is bound to the therapeutics. Hence, the particles possibly are opening an insight into drug distribution in the tumor region directly after administration.