Establishment of a biophysical model to optimize endoscopic targeting of magnetic nanoparticles for cancer treatment

Abstract

Superparamagnetic iron oxide nanoparticles (SPION) may be used for local tumor treatment by coupling them to a drug and accumulating them locally with magnetic field traps, that is, a combination of permanent magnets and coils. Thereafter, an alternating magnetic field generates heat which may be used to release the thermosensitively bound drug and for hyperthermia. Until today, only superficial tumors can be treated with this method. Our aim was to transfer this method into an endoscopic setting to also reach the majority of tumors located inside the body. To find the ideal endoscopic magnetic field trap, which accumulates the most SPION, we first developed a biophysical model considering anatomical as well as physical conditions. Entities of choice were esophageal and prostate cancer. The magnetic susceptibilities of different porcine and rat tissues were measured with a superconducting quantum interference device. All tissues showed diamagnetic behavior. The evaluation of clinical data (computed tomography scan, endosonography, surgical reports, pathological evaluation) of patients gave insight into the topographical relationship between the tumor and its surroundings. Both were used to establish the biophysical model of the tumors and their surroundings, closely mirroring the clinical situation, in which we could virtually design, place and evaluate different electromagnetic coil configurations to find optimized magnetic field traps for each tumor entity. By simulation, we could show that the efficiency of the magnetic field traps can be enhanced by 38-fold for prostate and 8-fold for esophageal cancer. Therefore, our approach of endoscopic targeting is an improvement of the magnetic drug-targeting setups for SPION tumor therapy as it holds the possibility of reaching tumors inside the body in a minimal-invasive way. Future animal experiments must prove these findings in vivo.

The Use of Alternative Strategies for Enhanced Nanoparticle Delivery to Solid Tumors

“…Accordingly, Roeth and colleagues aimed at translating this strategy to an endoscopic setting and reach tumors deep within the body. 242 They built a biophysical model to find the ideal endoscopic magnetic field trap that accumulates the most SPION. By simulation, they were able to enhance the efficiency of the magnetic field traps by 38-fold in prostate and 8-fold in esophageal cancer models.…”

“…Their method was able to reach tumors inside the body in a minimal-invasive way. 242 In another study, the group of Zhang 243 developed a novel real-time imaging-based guidance system with the aim of improving SPION transport across the BBB and into brain tumor regions. 243 They used an electromagnetic actuator and low-amplitude-excitation-field magnetic particle imaging (MPI) for the simultaneous noninvasive NM guiding and tracking inside a tube.…”

Combining Bulk Temperature and Nanoheating Enables Advanced Magnetic Fluid Hyperthermia Efficacy on Pancreatic Tumor Cells

“…Such low concentrations were achieved for a mouse tumor model using permanent magnets. Most promising recent developments showed that by using an endoscopic setting of magnetic targeting the target efficiency could be enhanced by a factor of 40 28 . Consequently, for tumors that can be reached endoscopically, such as PDAC, the MNP concentration inside the tumor could be drastically enhanced in the future using magnetic targeting settings.…”

The Potential of Magnetic Nanoparticles for Diagnosis and Treatment of Cancer Based on Body Magnetic Field and Organ-on-the-Chip

“…The physical absorption and chemical bonding have been used for loading of different molecules on organic and inorganic bases: the tumor-recognition moieties, 71,72 cell-penetrating peptides for MRI applications, 73,74 as well as enzymes, 75 genes, 76-80 growth factors, 81,82 radionucleotides, 83,84 drugs, 85,86 tamoxifen, 87 cefradine, 88 ammonium glycyrrhizinatezz, 89 fludarabine, 90 cisplatin and gemcitabine, 91 amethopterin, 88,92 mitomycin, 93 paclitaxel, 94,95 diclofenac sodium, 96,97 and Adriamycin 98 for drug delivery applications (Figures 2 and 3). 99…”