Prospects from Diagnosis to Treatment in Cancer Using Magnetic Methods

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Methods and Technologies Development".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 44167

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Guest Editor
Graduate School of Agricultural and Life Science, University of Tokyo, Tokyo, Japan
Interests: cancer treatment; experimental pathology; regenerative medicine
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Guest Editor
Graduate School of Engineering, University of Tokyo, Tokyo, Japan
Interests: bio-magnetism; bio-engineering; medical device

Special Issue Information

Dear colleagues,

Many cancer diagnosis and treatment modalities have been developed over time, among which radioisotopes have been widely used. Recently, with the application of magnetic nanoparticles, a wide range of non-invasive diagnosis and treatment methods using magnetic techniques have attracted attention.

This topic introduces lymph node biopsy with a magnetic probe for the treatment of cancer, rapid immunostaining using magnetic nanoparticles in pathological diagnosis, cancer imaging with MRI (magnetic resonance imaging)/MPI (magnetic particle imaging), magnetic hyperthermia for cancer treatment, and development of magnetic nanoparticles.

Prof. Moriaki Kusakabe
Dr. Akihiro Kuwahata
Guest Editors

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Keywords

  • cancer diagnosis and treatment
  • magnetic technique
  • lymph node biopsy
  • rapid immunostaining
  • cancer imaging
  • magnetic resonance imaging
  • magnetic particle imaging
  • magnetic hyperthermia

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Published Papers (12 papers)

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Research

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13 pages, 3368 KiB  
Article
A Comprehensive Grading System for a Magnetic Sentinel Lymph Node Biopsy Procedure in Head and Neck Cancer Patients
by Eliane R. Nieuwenhuis, Barry Kolenaar, Jurrit J. Hof, Joop van Baarlen, Alexander J. M. van Bemmel, Anke Christenhusz, Tom W. J. Scheenen, Bernard ten Haken, Remco de Bree and Lejla Alic
Cancers 2022, 14(3), 678; https://doi.org/10.3390/cancers14030678 - 28 Jan 2022
Cited by 3 | Viewed by 2925
Abstract
A magnetic sentinel lymph node biopsy ((SLN)B) procedure has recently been shown feasible in oral cancer patients. However, a grading system is absent for proper identification and classification, and thus for clinical reporting. Based on data from eight complete magnetic SLNB procedures, we [...] Read more.
A magnetic sentinel lymph node biopsy ((SLN)B) procedure has recently been shown feasible in oral cancer patients. However, a grading system is absent for proper identification and classification, and thus for clinical reporting. Based on data from eight complete magnetic SLNB procedures, we propose a provisional grading system. This grading system includes: (1) a qualitative five-point grading scale for MRI evaluation to describe iron uptake by LNs; (2) an ex vivo count of resected SLN with a magnetic probe to quantify iron amount; and (3) a qualitative five-point grading scale for histopathologic examination of excised magnetic SLNs. Most SLNs with iron uptake were identified and detected in level II. In this level, most variance in grading was seen for MRI and histopathology; MRI and medullar sinus were especially highly graded, and cortical sinus was mainly low graded. On average 82 ± 58 µg iron accumulated in harvested SLNs, and there were no significant differences in injected tracer dose (22.4 mg or 11.2 mg iron). In conclusion, a first step was taken in defining a comprehensive grading system to gain more insight into the lymphatic draining system during a magnetic SLNB procedure. Full article
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11 pages, 547 KiB  
Article
A Propensity Score Matched Analysis of Superparamagnetic Iron Oxide versus Radioisotope Sentinel Node Biopsy in Breast Cancer Patients after Neoadjuvant Chemotherapy
by Zuzanna Pelc, Magdalena Skórzewska, Maria Kurylcio, Tomasz Nowikiewicz, Radosław Mlak, Katarzyna Sędłak, Katarzyna Gęca, Karol Rawicz-Pruszyński, Wojciech Zegarski, Wojciech P. Polkowski and Andrzej Kurylcio
Cancers 2022, 14(3), 676; https://doi.org/10.3390/cancers14030676 - 28 Jan 2022
Cited by 6 | Viewed by 2657
Abstract
The standard method for nodal staging in breast cancer (BC) patients after neoadjuvant chemotherapy (NAC) is sentinel lymph node biopsy (SLNB) with a radioisotope (RI) injection. However, SLNB after NAC results in high false-negative rates (FNR), and the RI method is restricted by [...] Read more.
The standard method for nodal staging in breast cancer (BC) patients after neoadjuvant chemotherapy (NAC) is sentinel lymph node biopsy (SLNB) with a radioisotope (RI) injection. However, SLNB after NAC results in high false-negative rates (FNR), and the RI method is restricted by nuclear medicine unit dependency. These limitations resulted in the development of the superparamagnetic iron oxide (SPIO) method, reducing FNR and presenting a comparable detection rate. This bi-institutional cohort comparison study aimed to assess the efficacy of SPIO and radioisotope SNLB in BC patients after NAC using Propensity Score Matching (PSM) analysis. The study group comprised 508 patients who underwent SLNB after NAC for ycT1-4N0M0 BC between 2013 and 2021 in two high volume centers. Data were retrieved from prospectively conducted databases. In the SPIO group, the median of retrieved sentinel lymph nodes (SLNs) was significantly higher than in the RI group (3 vs. 2; p < 0.0001). The SPIO method was associated with a significantly higher chance of retrieving at least three lymph nodes when compared to the RI method (71% vs. 11.3%; p < 0.0001). None of the analyzed demographic and clinical variables had a statistically significant influence on the efficacy of SLNs retrieval in the RI group, while in the SPIO group, patients with ≥three harvested SLNs had lower weight and decreased BMI. Based on this PSM analysis, SPIO-guided SLNB allowed the efficient retrieval and detection of SLNs in BC patients after NAC compared to RI. Full article
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12 pages, 1414 KiB  
Article
Magnetometer-Guided Sentinel Lymph Node Dissection in Prostate Cancer: Rate of Lymph Node Involvement Compared with Radioisotope Marking
by Svenja Engels, Bianca Michalik, Luca-Marie Meyer, Lena Nemitz, Friedhelm Wawroschek and Alexander Winter
Cancers 2021, 13(22), 5821; https://doi.org/10.3390/cancers13225821 - 20 Nov 2021
Cited by 5 | Viewed by 2164
Abstract
Sentinel pelvic lymph node dissection (sPLND) enables the targeted removal of lymph nodes (LNs) bearing the highest metastasis risk. In prostate cancer (PCa), sPLND alone or combined with extended PLND (ePLND) reveals more LN metastases along with detecting sentinel LNs (SLNs) outside the [...] Read more.
Sentinel pelvic lymph node dissection (sPLND) enables the targeted removal of lymph nodes (LNs) bearing the highest metastasis risk. In prostate cancer (PCa), sPLND alone or combined with extended PLND (ePLND) reveals more LN metastases along with detecting sentinel LNs (SLNs) outside the conventional ePLND template. To overcome the disadvantages of radioisotope-guided sPLND in PCa treatment, magnetometer-guided sPLND applying superparamagnetic iron oxide nanoparticles as a tracer was established. This retrospective study compared the nodal staging ability between magnetometer- and radioisotope-guided sPLNDs. We analyzed data of PCa patients undergoing radical prostatectomy and magnetometer- (848 patients, 2015–2021) or radioisotope-guided (2092 patients, 2006–2015) sPLND. To reduce heterogeneity among cohorts, we performed propensity score matching and compared data considering sentinel nomogram-based probabilities for LN involvement (LNI). Magnetometer- and radioisotope-guided sPLNDs had SLN detection rates of 98.12% and 98.09%, respectively; the former detected more SLNs per patient. The LNI rates matched nomogram-based predictions in both techniques equally well. Approximately 7% of LN metastases were detected outside the conventional ePLND template. Thus, we confirmed the reliability of magnetometer-guided sPLND in nodal staging, with results comparable with or better than radioisotope-guided sPLND. Our findings highlight the importance of the sentinel technique for detecting LN metastases in PCa. Full article
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19 pages, 5108 KiB  
Article
Dual Targeting with Cell Surface Electrical Charge and Folic Acid via Superparamagnetic Fe3O4@Cu2–xS for Photothermal Cancer Cell Killing
by Zicheng Deng, Jou Lin, Sergey L. Bud’ko, Brent Webster, Tanya V. Kalin, Vladimir V. Kalinichenko and Donglu Shi
Cancers 2021, 13(21), 5275; https://doi.org/10.3390/cancers13215275 - 21 Oct 2021
Cited by 17 | Viewed by 3360
Abstract
A major challenge in cancer therapy is to achieve high cell targeting specificity for the highest therapeutic efficacy. Two major approaches have been shown to be quite effective, namely, (1) bio-marker mediated cell targeting, and (2) electrical charge driven cell binding. The former [...] Read more.
A major challenge in cancer therapy is to achieve high cell targeting specificity for the highest therapeutic efficacy. Two major approaches have been shown to be quite effective, namely, (1) bio-marker mediated cell targeting, and (2) electrical charge driven cell binding. The former utilizes the tumor-specific moieties on nano carrier surfaces for active targeting, while the latter relies on nanoparticles binding onto the cancer cell surfaces due to differences in electrical charge. Cancer cells are known for their hallmark metabolic pattern: high rates of glycolysis that lead to negatively charged cell surfaces. In this study, the nanoparticles of Fe3O4@Cu2–xS were rendered positively charged by conjugating their surfaces with different functional groups for strong electrostatic binding onto the negatively-charged cancer cells. In addition to the positively charged surfaces, the Fe3O4@Cu2–xS nanoparticles were also modified with folic acid (FA) for biomarker-based cell targeting. The dual-targeting approach synergistically utilizes the effectiveness of both charge- and biomarker-based cell binding for enhanced cell targeting. Further, these superparamagnetic Fe3O4@Cu2–xS nanoparticles exhibit much stronger IR absorptions compared to Fe3O4, therefore much more effective in photothermal therapy. Full article
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14 pages, 1264 KiB  
Article
Optimization of SPIO Injection for Sentinel Lymph Node Dissection in a Rat Model
by Mirjam C. L. Peek, Kohei Saeki, Kaichi Ohashi, Shinichi Chikaki, Rose Baker, Takayuki Nakagawa, Moriaki Kusakabe, Michael Douek and Masaki Sekino
Cancers 2021, 13(19), 5031; https://doi.org/10.3390/cancers13195031 - 8 Oct 2021
Cited by 7 | Viewed by 2121
Abstract
The magnetic technique, consisting of a magnetic tracer and a handheld magnetometer, is a promising alternative technique for sentinel lymph node dissection (SLND) and was shown to be non-inferior to the standard technique in terms of identification rates. In this study, injection characteristics [...] Read more.
The magnetic technique, consisting of a magnetic tracer and a handheld magnetometer, is a promising alternative technique for sentinel lymph node dissection (SLND) and was shown to be non-inferior to the standard technique in terms of identification rates. In this study, injection characteristics (iron dose, dilution, time course and massaging) were evaluated to optimize magnetic tracer uptake in the sentinel lymph nodes (SLN) in a rat hindleg model. 202 successful SLNDs were performed. Iron uptake in the SLN is proportional (10% utilization rate) to the injection dose between 20 and 200 μg, showing a plateau uptake of 80 μg in the SLN around 1000 μg injection. Linear regression showed that time had a higher impact than dilution, on the SLN iron uptake. Massaging showed no significant change in iron uptake. The amount of residual iron at the injection site was also proportional to the injection dose without any plateau. Time was a significant factor for wash-out of residual iron. From these results, preoperative injection may be advantageous for SLN detection as well as reduction in residual iron at the injection site by potential decrease in required injection dose. Full article
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13 pages, 1782 KiB  
Article
Magnetic-Guided Axillary UltraSound (MagUS) Sentinel Lymph Node Biopsy and Mapping in Patients with Early Breast Cancer. A Phase 2, Single-Arm Prospective Clinical Trial
by Allan Jazrawi, Eirini Pantiora, Shahin Abdsaleh, Daniel Vasiliu Bacovia, Staffan Eriksson, Henrik Leonhardt, Fredrik Wärnberg and Andreas Karakatsanis
Cancers 2021, 13(17), 4285; https://doi.org/10.3390/cancers13174285 - 25 Aug 2021
Cited by 11 | Viewed by 3935
Abstract
Lymph Node Dissection (SLND) is standard of care for diagnosing sentinel lymph node (SLN) status in patients with early breast cancer. Study aim was to determine whether the combination of Superparamagnetic iron oxide nanoparticles (SPIO) MRI-lymphography (MRI-LG) and a Magnetic-guided Axillary UltraSound (MagUS) [...] Read more.
Lymph Node Dissection (SLND) is standard of care for diagnosing sentinel lymph node (SLN) status in patients with early breast cancer. Study aim was to determine whether the combination of Superparamagnetic iron oxide nanoparticles (SPIO) MRI-lymphography (MRI-LG) and a Magnetic-guided Axillary UltraSound (MagUS) with biopsy can allow for minimally invasive, axillary evaluation to de-escalate surgery. Patients were injected with 2 mL of SPIO and underwent MRI-LG for SN mapping. Thereafter MagUS and core needle biopsy (CNB) were performed. Patients planned for neoadjuvant treatment, the SLN was clipped and SLND was performed after neoadjuvant with the addition of isotope. During surgery, SLNs were controlled for signs of previous biopsy or clip. The primary endpoint was MagUS SLN detection rate, defined as successful SLN detection of at least one SLN of those retrieved in SLND. In 79 patients, 48 underwent upfront surgery, 12 received neoadjuvant and 19 had recurrent cancer. MagUS traced the SLN in all upfront and neoadjuvant cases, detecting all patients with macrometastases (n = 10). MagUS missed only one micrometastasis, outperforming baseline axillary ultrasound AUS (AUC: 0.950 vs. 0.508, p < 0.001) and showing no discordance to SLND (p = 1.000). MagUS provides the niche for minimally invasive axillary mapping that can reduce diagnostic surgery. Full article
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22 pages, 22749 KiB  
Article
Citrate-Coated Superparamagnetic Iron Oxide Nanoparticles Enable a Stable Non-Spilling Loading of T Cells and Their Magnetic Accumulation
by Philipp Boosz, Felix Pfister, Rene Stein, Bernhard Friedrich, Lars Fester, Julia Band, Marina Mühlberger, Eveline Schreiber, Stefan Lyer, Diana Dudziak, Christoph Alexiou and Christina Janko
Cancers 2021, 13(16), 4143; https://doi.org/10.3390/cancers13164143 - 17 Aug 2021
Cited by 17 | Viewed by 4084
Abstract
T cell infiltration into a tumor is associated with a good clinical prognosis of the patient and adoptive T cell therapy can increase anti-tumor immune responses. However, immune cells are often excluded from tumor infiltration and can lack activation due to the immune-suppressive [...] Read more.
T cell infiltration into a tumor is associated with a good clinical prognosis of the patient and adoptive T cell therapy can increase anti-tumor immune responses. However, immune cells are often excluded from tumor infiltration and can lack activation due to the immune-suppressive tumor microenvironment. To make T cells controllable by external forces, we loaded primary human CD3+ T cells with citrate-coated superparamagnetic iron oxide nanoparticles (SPIONs). Since the efficacy of magnetic targeting depends on the amount of SPION loading, we investigated how experimental conditions influence nanoparticle uptake and viability of cells. We found that loading in the presence of serum improved both the colloidal stability of SPIONs and viability of T cells, whereas stimulation with CD3/CD28/CD2 and IL-2 did not influence nanoparticle uptake. Furthermore, SPION loading did not impair cytokine secretion after polyclonal stimulation. We finally achieved 1.4 pg iron loading per cell, which was both located intracellularly in vesicles and bound to the plasma membrane. Importantly, nanoparticles did not spill over to non-loaded cells. Since SPION-loading enabled efficient magnetic accumulation of T cells in vitro under dynamic conditions, we conclude that this might be a good starting point for the investigation of in vivo delivery of immune cells. Full article
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10 pages, 2716 KiB  
Article
Magnetically Guided Localization Using a Guiding-Marker System® and a Handheld Magnetic Probe for Nonpalpable Breast Lesions: A Multicenter Feasibility Study in Japan
by Tomoko Kurita, Kanae Taruno, Seigo Nakamura, Hiroyuki Takei, Katsutoshi Enokido, Takashi Kuwayama, Yoko Kanada, Sadako Akashi-Tanaka, Misaki Matsuyanagi, Meishi Hankyo, Keiko Yanagihara, Takashi Sakatani, Kentaro Sakamaki, Akihiro Kuwahata, Masaki Sekino and Moriaki Kusakabe
Cancers 2021, 13(12), 2923; https://doi.org/10.3390/cancers13122923 - 11 Jun 2021
Cited by 11 | Viewed by 3135
Abstract
Accurate pre-operative localization of nonpalpable lesions plays a pivotal role in guiding breast-conserving surgery (BCS). In this multicenter feasibility study, nonpalpable breast lesions were localized using a handheld magnetic probe (TAKUMI) and a magnetic marker (Guiding-Marker System®). The magnetic marker was [...] Read more.
Accurate pre-operative localization of nonpalpable lesions plays a pivotal role in guiding breast-conserving surgery (BCS). In this multicenter feasibility study, nonpalpable breast lesions were localized using a handheld magnetic probe (TAKUMI) and a magnetic marker (Guiding-Marker System®). The magnetic marker was preoperatively placed within the target lesion under ultrasound or stereo-guidance. Additionally, a dye was injected subcutaneously to indicate the extent of the tumor excision. Surgeons checked for the marker within the lesion using a magnetic probe. The magnetic probe could detect the guiding marker and accurately localize the target lesion intraoperatively. All patients with breast cancer underwent wide excision with a safety margin of ≥5 mm. The presence of the guiding-marker within the resected specimen was the primary outcome and the pathological margin status and re-excision rate were the secondary outcomes. Eighty-seven patients with nonpalpable lesions who underwent BCS, from January to March of 2019 and from January to July of 2020, were recruited. The magnetic marker was detected in all resected specimens. The surgical margin was positive only in 5/82 (6.1%) patients; these patients underwent re-excision. This feasibility study demonstrated that the magnetic guiding localization system is useful for the detection and excision of nonpalpable breast lesions. Full article
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Review

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17 pages, 3757 KiB  
Review
Application of Magnetic Nanoparticles for Rapid Detection and In Situ Diagnosis in Clinical Oncology
by Tatsuya Onishi, Kisyo Mihara, Sachiko Matsuda, Satoshi Sakamoto, Akihiro Kuwahata, Masaki Sekino, Moriaki Kusakabe, Hiroshi Handa and Yuko Kitagawa
Cancers 2022, 14(2), 364; https://doi.org/10.3390/cancers14020364 - 12 Jan 2022
Cited by 17 | Viewed by 3950
Abstract
Screening, monitoring, and diagnosis are critical in oncology treatment. However, there are limitations with the current clinical methods, notably the time, cost, and special facilities required for radioisotope-based methods. An alternative approach, which uses magnetic beads, offers faster analyses with safer materials over [...] Read more.
Screening, monitoring, and diagnosis are critical in oncology treatment. However, there are limitations with the current clinical methods, notably the time, cost, and special facilities required for radioisotope-based methods. An alternative approach, which uses magnetic beads, offers faster analyses with safer materials over a wide range of oncological applications. Magnetic beads have been used to detect extracellular vesicles (EVs) in the serum of pancreatic cancer patients with statistically different EV levels in preoperative, postoperative, and negative control samples. By incorporating fluorescence, magnetic beads have been used to quantitatively measure prostate-specific antigen (PSA), a prostate cancer biomarker, which is sensitive enough even at levels found in healthy patients. Immunostaining has also been incorporated with magnetic beads and compared with conventional immunohistochemical methods to detect lesions; the results suggest that immunostained magnetic beads could be used for pathological diagnosis during surgery. Furthermore, magnetic nanoparticles, such as superparamagnetic iron oxide nanoparticles (SPIONs), can detect sentinel lymph nodes in breast cancer in a clinical setting, as well as those in gallbladder cancer in animal models, in a surgery-applicable timeframe. Ultimately, recent research into the applications of magnetic beads in oncology suggests that the screening, monitoring, and diagnosis of cancers could be improved and made more accessible through the adoption of this technology. Full article
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27 pages, 6538 KiB  
Review
Magnetic Particle Imaging: An Emerging Modality with Prospects in Diagnosis, Targeting and Therapy of Cancer
by Zhi Wei Tay, Prashant Chandrasekharan, Benjamin D. Fellows, Irati Rodrigo Arrizabalaga, Elaine Yu, Malini Olivo and Steven M. Conolly
Cancers 2021, 13(21), 5285; https://doi.org/10.3390/cancers13215285 - 21 Oct 2021
Cited by 31 | Viewed by 5347
Abstract
Background: Magnetic Particle Imaging (MPI) is an emerging imaging modality for quantitative direct imaging of superparamagnetic iron oxide nanoparticles (SPION or SPIO). With different physics from MRI, MPI benefits from ideal image contrast with zero background tissue signal. This enables clear visualization of [...] Read more.
Background: Magnetic Particle Imaging (MPI) is an emerging imaging modality for quantitative direct imaging of superparamagnetic iron oxide nanoparticles (SPION or SPIO). With different physics from MRI, MPI benefits from ideal image contrast with zero background tissue signal. This enables clear visualization of cancer with image characteristics similar to PET or SPECT, but using radiation-free magnetic nanoparticles instead, with infinite-duration reporter persistence in vivo. MPI for cancer imaging: demonstrated months of quantitative imaging of the cancer-related immune response with in situ SPION-labelling of immune cells (e.g., neutrophils, CAR T-cells). Because MPI suffers absolutely no susceptibility artifacts in the lung, immuno-MPI could soon provide completely noninvasive early-stage diagnosis and treatment monitoring of lung cancers. MPI for magnetic steering: MPI gradients are ~150 × stronger than MRI, enabling remote magnetic steering of magneto-aerosol, nanoparticles, and catheter tips, enhancing therapeutic delivery by magnetic means. MPI for precision therapy: gradients enable focusing of magnetic hyperthermia and magnetic-actuated drug release with up to 2 mm precision. The extent of drug release from the magnetic nanocarrier can be quantitatively monitored by MPI of SPION’s MPS spectral changes within the nanocarrier. Conclusion: MPI is a promising new magnetic modality spanning cancer imaging to guided-therapy. Full article
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31 pages, 3058 KiB  
Review
Understanding MNPs Behaviour in Response to AMF in Biological Milieus and the Effects at the Cellular Level: Implications for a Rational Design That Drives Magnetic Hyperthermia Therapy toward Clinical Implementation
by David Egea-Benavente, Jesús G. Ovejero, María del Puerto Morales and Domingo F. Barber
Cancers 2021, 13(18), 4583; https://doi.org/10.3390/cancers13184583 - 12 Sep 2021
Cited by 37 | Viewed by 5733
Abstract
Hyperthermia has emerged as a promising alternative to conventional cancer therapies and in fact, traditional hyperthermia is now commonly used in combination with chemotherapy or surgery during cancer treatment. Nevertheless, non-specific application of hyperthermia generates various undesirable side-effects, such that nano-magnetic hyperthermia has [...] Read more.
Hyperthermia has emerged as a promising alternative to conventional cancer therapies and in fact, traditional hyperthermia is now commonly used in combination with chemotherapy or surgery during cancer treatment. Nevertheless, non-specific application of hyperthermia generates various undesirable side-effects, such that nano-magnetic hyperthermia has arisen a possible solution to this problem. This technique to induce hyperthermia is based on the intrinsic capacity of magnetic nanoparticles to accumulate in a given target area and to respond to alternating magnetic fields (AMFs) by releasing heat, based on different principles of physics. Unfortunately, the clinical implementation of nano-magnetic hyperthermia has not been fluid and few clinical trials have been carried out. In this review, we want to demonstrate the need for more systematic and basic research in this area, as many of the sub-cellular and molecular mechanisms associated with this approach remain unclear. As such, we shall consider here the biological effects that occur and why this theoretically well-designed nano-system fails in physiological conditions. Moreover, we will offer some guidelines that may help establish successful strategies through the rational design of magnetic nanoparticles for magnetic hyperthermia. Full article
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21 pages, 945 KiB  
Review
In Vitro Magnetic Techniques for Investigating Cancer Progression
by Sarah Libring, Ángel Enríquez, Hyowon Lee and Luis Solorio
Cancers 2021, 13(17), 4440; https://doi.org/10.3390/cancers13174440 - 3 Sep 2021
Cited by 6 | Viewed by 3255
Abstract
Worldwide, there are currently around 18.1 million new cancer cases and 9.6 million cancer deaths yearly. Although cancer diagnosis and treatment has improved greatly in the past several decades, a complete understanding of the complex interactions between cancer cells and the tumor microenvironment [...] Read more.
Worldwide, there are currently around 18.1 million new cancer cases and 9.6 million cancer deaths yearly. Although cancer diagnosis and treatment has improved greatly in the past several decades, a complete understanding of the complex interactions between cancer cells and the tumor microenvironment during primary tumor growth and metastatic expansion is still lacking. Several aspects of the metastatic cascade require in vitro investigation. This is because in vitro work allows for a reduced number of variables and an ability to gather real-time data of cell responses to precise stimuli, decoupling the complex environment surrounding in vivo experimentation. Breakthroughs in our understanding of cancer biology and mechanics through in vitro assays can lead to better-designed ex vivo precision medicine platforms and clinical therapeutics. Multiple techniques have been developed to imitate cancer cells in their primary or metastatic environments, such as spheroids in suspension, microfluidic systems, 3D bioprinting, and hydrogel embedding. Recently, magnetic-based in vitro platforms have been developed to improve the reproducibility of the cell geometries created, precisely move magnetized cell aggregates or fabricated scaffolding, and incorporate static or dynamic loading into the cell or its culture environment. Here, we will review the latest magnetic techniques utilized in these in vitro environments to improve our understanding of cancer cell interactions throughout the various stages of the metastatic cascade. Full article
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