Experimental study on magnetic drug targeting in treating cholangiocarcinoma based on internal magnetic fields

Objective: To evaluate the effect of magnetic nanoparticle containing 5-fluorouracil (5-FU) targeting in treating chol- angiocarcinoma based on internal magnetic fields built inside the tumor. Methods: 32 nude mice of BABL/C bearing ectopic tumor were built by subcutaneouly injecting cholangiocarcinoma cell line QBC 939. Three weeks after tumor inoculation, the animal models were divided equally into four groups at random including: (a) group A, consisting of internal magnetic field built by magnetic biliary stent wires inserted into tumor tissue and receiving magnetic nanoparticles containing 5-FU administered via tail vein injection at 250 mg/kg for consecutive five days; (b) group B, receiving placebo (sodium chloride); (c) group C, receiving pure magnetic biliary stent wires without the applying of magnetic nanoparticles; (d) group D, consisting of external magnetic fields and the same treatment of magnetic nanoparticles containing 5-FU as group A. The tumor volumes were measured every 3 days, totally six times from treatment started. Tumor tissues were observed by transmission electron microscope when the nude mice were killed after the observation period. Results: The experimental group (group A) showed significantly therapeutic efficacy. Moreover, apoptosis of tumor cells could be easily detected in this group. Conclusion: Magnetic particles containing 5-FU combined with internal magnetic field can effectively treat cholangiocarcinoma, and its therapeutic efficacy is better than that of the traditional method based on external magnetic fields.

Hydrodynamic modeling of ferrofluid flow in magnetic targeting drug delivery

Among the proposed techniques for delivering drugs to specific locations within human body, magnetic drug targeting prevails due to its non-invasive character and its high targeting efficiency. Magnetic targeting drug delivery is a method of carrying drug-loaded magnetic nanoparticles to a target tissue target under the applied magnetic field. This method increases the drug concentration in the target while reducing the adverse side-effects. Although there have been some theoretical analyses for magnetic drug targeting, very few researchers have addressed the hydrodynamic models of magnetic fluids in the blood vessel. A mathematical model is presented to describe the hydrodynamics of ferrofiuids as drug carriers flowing in a blood vessel under the applied magnetic field. In this model, magnetic force and asymmetrical force are added, and an angular momentum equation of magnetic nanoparticles in the applied magnetic field is modeled. Engineering approximations are achieved by retaining the physically most significant items in the model due to the mathematical complexity of the motion equations. Numerical simulations are performed to obtain better insight into the theoretical model with computational fluid dynamics. Simulation results demonstrate the important parameters leading to adequate drug delivery to the target site depending on the magnetic field intensity, which coincident with those of animal experiments. Results of the analysis provide important information and suggest strategies for improving delivery in clinical application.

Process Modeling of Ferrofluids Flow for Magnetic Targeting Drug Delivery

Among the proposed techniques for delivering drugs to specific sites within the human body, magnetic targeting drug delivery surpasses due to its non-invasive character and its high targeting efficiency. Although there have been some analyses theoretically for magnetic drug targeting, very few researchers have addressed the hydrodynamic models of magnetic fluids in the blood vessel of human body. This paper presents a mathematical model to describe the hydrodynamics of ferrofluids as drug carriers flowing in a blood vessel under the applied magnetic field. A 3D flow field of magnetic particles in a blood vessel model is numerically simulated in order to further understand clinical application of magnetic targeting drug delivery. Simulation results show that magnetic nanoparticles can be enriched in a target region depending on the applied magnetic field intensity. Magnetic resonance imaging confirms the enrichment of ferrofluids in a desired body tissue of Sprague-Dawley rats. The simulation results coincide with those animal experiments. Results of the analysis provide the important information and can suggest strategies for improving delivery in favor of the clinical application.

Acid-degradable gadolinium-based nanoscale coordination polymer： A potential platform for targeted drug delivery and potential magnetic resonance imaging

During conventional chemotherapy for cancer, nonspecific drug distribution, which causes serious side effects in normal tissues, is a serious limitation. Thus, it is desirable to develop a tumor or intracellular microenvironment-responsive nanosystem for targeted and on-demand drug release. In the present study, we engineered an intelligent pH-activatable nanosystem, in which a gadolinium- doxorubicin-loaded nanoscale coordination polymer （Gd-Dox NCPs） was the core and hyaluronic acid was the targeting shell. Taking advantage of CD44 receptor-mediated recognition, the nanoparticles were internalized selectively into human cervical carcinoma （HeLa） cells, and trapped within acidic compartments where the fluorescence of Dox recovered, along with the acid dismantling of the Gd NCPs, allowing real-time monitoring of drug release. In vitro experiments also showed that the Gd NCPs present enhanced T1 signals after acid-triggered degradation, suggesting their potential use as contrast agents for magnetic resonance imaging. Such nanocarriers, which feature high biodegradation, selective targeting ability, and rapid response to stimulus, demonstrated enhanced therapeutic efficacy in targeted cancer cells and ＂turned on＂T1 signals in vitro, showing great promise for diagnosis and treatment.