Detection of the characteristic magnetic signal of paclitaxel and its application in the inhibition of glioma cells

Abstract

Glioma, a type of brain tumor, is one of the most challenging cancers for human beings due to its genetic heterogeneity, high recurrence rate and difficulty of effective treatment. To explore a novel treatment method for glioma, a scientific hypothesis was proposed that a chemical substance or biological agent may generate a characteristic magnetic signal, and this signal is the fundamental reason that the chemical substance or biological agent works for cancer treatment. Based on this hypothesis, a superconducting quantum interference device (SQUID) using the stochastic resonance (SR) method was established, and the characteristic magnetic signal of paclitaxel was detected and clearly visualized for the first time. Then, cell experimental results demonstrated that the detected characteristic magnetic signal of paclitaxel was as effective as paclitaxel for the inhibition of glioma cells. Our study suggested that the application of paclitaxel's characteristic magnetic signal might provide an ideal treatment direction for glioma patients due to its lack of side effects, high focusable penetration and effectiveness.

Graphical abstract

1. Introduction

Brain tumors ranked ninth in cancer incidence in China according to the latest national statistics in 2020 [1]. Among brain tumors, glioma is attracting increasing attention due to its genetic heterogeneity, high recurrence rate and difficulty of effective treatment. The incidence of glioma is increasing yearly, and surgical resection is currently the first approach for its treatment. Subsequently, patients need to receive comprehensive treatment, such as radiotherapy, chemotherapy, immunotherapy and targeted therapy [1]. Among them, chemotherapy is the main method used in clinical practice. Although the efficacy of chemotherapy is very limited, there is still no treatment that can surpass classical chemotherapy according to the clinical statistics of the last 15 years. For patients with high-grade glioma, i.e., glioblastoma, the median survival time is only 12–14 months. At the same time, chemotherapy has considerable side effects and poor tolerance and is highly affected by the blood‒brain barrier. In the past 30 years, there has been no significant improvement in the treatment of glioma [2,3].

In recent years, with the rise of electric field therapy, physical field therapy has been considered a new direction for glioma treatment [4]. Electric field therapy is a noninvasive method that uses an oscillating electric field to impact the mitosis process of glioma cells. The impact of the blood‒brain barrier on electric field therapy is less than that on chemotherapy, and the side effects of this method are significantly decreased. Currently, electric field therapy is the only new treatment method that has obtained permission for clinical use and is able to prolong the survival time of glioma patients. According to the reported results, electric field therapy may, on average, bring 5 months of tumor remission to glioma patients [4]. However, electric field therapy also has the following disadvantages. First, the treatment device needs to be worn for more than 18 h every day, which adds significant inconvenience to the patient's normal life. Second, the patient's hair must be completely removed, and the treatment device may cause damage to the patient's scalp. Third, the electric field energy for the treatment cannot be well focused, and its penetration is highly affected by the tissues in the path of field energy, which significantly impacts the treatment effectiveness of the method. Fourth, the cost of electric field therapy is still high, at a level of millions of RMB per year.

By using a physical energy field, electric field therapy provides a new direction for the treatment of glioma. Compared with electric fields, magnetic fields are another widely present physical field [5]. The expected advantages of using magnetic energy for glioma treatment are as follows. First, the energy of the magnetic field is not known to damage human beings. Second, it has strong penetration into human tissues and the skull, and thus, the blood‒brain barrier is not a problem. Third, the energy distribution of the magnetic field can be well controlled and is not affected by tissues, which means that the energy can be focused on the glioma region. Fourth, the generation of a magnetic field can be convenient and cost-effective. If effective treatment can be achieved, the use of magnetic field therapy as a new treatment method for glioma may be a subversive technology with tremendous clinical value.

At present, clinical treatment research based on electromagnetic fields is mainly focused on rotator cuff tendinitis, nonhealing fractures, urinary incontinence, depression, anxiety, type 2 diabetes and other chronic diseases [6]. In the United States, a research team from Nativis company performed a study of cancer treatment based on the concept of using a magnetic field to simulate the effects of drugs [7]. The principal hypothesis is that each chemical substance or biological agent generates a specific magnetic field signal, which is the fundamental reason for the effectiveness of the chemical substance or biological agent in applications such as cancer treatment. Based on this hypothesis, drugs for cancer treatment may also generate such specific magnetic field signals. If the hypothesis is proven to be correct and these signals can be detected, we may directly apply the signals to cancer, and it should achieve the same inhibition effect as drugs on cancer cells combined with the advantages of magnetic field therapy. However, this hypothesis has not yet been validated, and such a specific magnetic field signal is still mysterious. The purpose of our study here is to explicitly detect such a specific magnetic field signal and systematically validate the hypothesis by applying the potentially detected magnetic signal to the inhibition of glioma cells. The potentially detected magnetic signals of drugs are called the characteristic magnetic signals of drugs in our study. Since paclitaxel is a widely utilized drug that has been proven to work well for several cancer treatments [8], it was selected as the first target drug in our study for related research.

2. Methods and materials

The proposed approach in our study mainly consists of two procedures: one to detect the characteristic magnetic signal of paclitaxel and the other to apply the detected signal to the target of glioma cells.

2.1. Establishment of the required SQUID system

Since the characteristic magnetic signal of a drug is expected to have a femto-tesla (fT) level, the detection system must have the corresponding sensitivity [9]. A superconducting quantum interference device (SQUID) is an extremely sensitive device for the detection of magnetic flux detection and physical quantities that can be converted to magnetic flux [9]. Based on the Josephson effect and the flux quantization effect, the SQUID can detect magnetic signals with intensity as low as the fT level.

Fig. 1 shows a schematic of our system for weak magnetic signal detection. The main part of this detection system is located in a magnetically shielded room, which can dramatically attenuate the Earth's magnetic field and the environmental magnetic interference, e.g., from electrical equipment. A low-noise liquid helium dewar provides the 4.2 K working temperature for the SQUID. A niobium-wire hand-wound superconducting second-order gradiometer, which is inductively coupled to SQUID, is used to pick up the magnetic signal of the sample. Since the magnetic signal of paclitaxel is extremely weak, the stochastic resonance method [10] is further applied to enhance the magnetic signal amplitude of paclitaxel in our study, as described in the next section. The solenoid and Helmholtz coil pair generate a white noise magnetic field and a static magnetic field, respectively, which are the two key conditions for stochastic resonance. The SQUID readout electronics and the intensity of the stochastic noise are controlled by a console that can communicate with a PC. The sampling rate of the 24-bit data acquisition card is set to 60 kHz.

Fig. 1.

Schematic diagram of the weak magnetic signal detection system.

2.2. The stochastic resonance method for signal enhancement

To detect a weak signal, the conventional processing approach is to reduce the noise level or improve the signal level. However, for the detection of the characteristic magnetic signal, the detailed characteristics of both noise and signal are completely unknown and difficult to quantify when utilizing the SQUID system. Moreover, the intrinsic signal-to-noise ratio (SNR) for the detection is too low to effectively investigate the target signal. Because of these conditions, it is necessary to have a method to enhance the SNR.

When a signal has periodic components, the SNR can be significantly improved by introducing noise with certain characteristics into the signal detecting system [10]. The added noise is stochastic with a relatively wide spectrum. The principle of this signal enhancing processing is that the periodic components of the signal might have resonant responses with some part of the introduced noise, and the resonant responses may transfer the noise's energy into the signal's corresponding components. Therefore, the signal can be precisely enhanced without knowing the detailed characteristics of either the detecting system's noise or the target signal. This signal processing method is called the stochastic resonance (SR) method [10].

The expected resonance for the signal enhancement occurs only under strict conditions for the entire detecting system, including the detected drug, which is paclitaxel in this case. The required conditions are for the purpose of making the detecting system theoretically contain at least two potential wells [10]. Only in this situation can the expected SR occur if the introduced stochastic noise has an appropriate intensity level [10]. However, in practice, it is impractical to theoretically calculate the required conditions for a quantitative evaluation of the occurring probability of SR since there are too many factors impacting the detection system that cannot be well quantitatively estimated. To overcome this difficulty in our study, we proposed and applied a method from a different and novel point of view.

As we already know, the fundamental effect of SR for the enhancement of a signal is the signal enhancement itself. From this point of view, if the signal enhancement can be detected, the SR can be considered to occur. Therefore, in our proposed method, the adjustable parameters for stimulating SR for the entire detecting system are first determined. Then, the search algorithm is applied in the parameter space. The effectiveness of SR enhancement for different parameter combinations is evaluated by quantifying the extent of the detectability of the potentially enhanced signal based on the acquired SQUID data. It can be seen that the proposed method avoids the difficulty of the system parameter estimation for SR and directly evaluates the extent of SR in the SR parameter space according to the detectability of the enhanced signal. Practically, in our study, if the difference between the target sample and the control sample can be clearly detected, SR appears to occur. In this way, the detection of the characteristic magnetic signal for paclitaxel becomes feasible.

There are two key SR parameters to adjust for stimulating SR in our study, namely, the stimulating stochastic magnetic noise and the bias magnetic field for the SQUID system. Other parameters of the detecting system are set to be consistent during the data acquisition periods. This may effectively constrain the size of the SR parameter space for the search algorithm.

2.3. The prepared solution of paclitaxel

Paclitaxel is a compound with antineoplastic activity extracted from the Pacific yew tree Taxus brevifolia [8]. Paclitaxel binds to tubulin and inhibits the disassembly of microtubules, thereby resulting in the inhibition of cell division. This agent also induces apoptosis by binding to and blocking the function of the apoptosis inhibitor protein Bcl-2 (B-cell leukemia 2). It currently plays an important role in the chemotherapeutic treatment of cancer and is the target drug for characteristic magnetic signal detection in our study.

A paclitaxel suspension (6 mg/ml, MedChemExpress, Company, Monmouth Junction, NJ, USA, Cat. No. HY-B0015) was dissolved in ultra-pure (UP) water for detection by the SQUID system. The samples to be detected (UP water as the control sample and paclitaxel in UP water as the target sample) were separately placed under the sensor of the established SQUID system. Then, the corresponding data were acquired for the paclitaxel and control samples.

2.4. Characteristic magnetic signal detection of paclitaxel

The established SQUID detection system utilizes a signal sampling rate of 60 kHz to record the characteristic magnetic signal. With one set of SR parameters, the recording time for one data point in our study is 120 min, which may guarantee the stationarity of the recorded signals. Two data sets are recorded for the paclitaxel and control samples under one set of SR parameters. Then, spectrum analysis of the two data sets is performed, and the spectrum difference is considered to represent the extent of SR for the characteristic magnetic signal enhancement. An apparent SR phenomenon with one set of adjustable SR parameters cannot be guaranteed to occur for signal enhancement. Therefore, our study uses a grid search algorithm to explore the potentially appropriate combinations of adjustable SR parameters for the SQUID detection system [11]. If the SR phenomenon is found to be explicitly stimulated in one set of recorded signals, the signal from the paclitaxel sample is then the detected characteristic magnetic signal of paclitaxel (CMSP), and the signal from the control sample is the corresponding magnetic signal of the control (MSC), which will be used for subsequent cell experiments.

2.5. The electronic system to emit the detected characteristic magnetic signal

Once we obtain the CMSP signal, an electronic system is necessary to transfer the signal and emit the corresponding magnetic signal energy to the biological target tissue, in this case, glioma cells. The established electronic system consists of four parts: the controlling general computer, the waveform generator, the wide-band amplifier and the Helmholtz coil. An oscilloscope is utilized to monitor the output signal of the system after the wide-band amplifier. Fig. 2 illustrates the established electronic system.

Fig. 2.

The electronic system that emits the detected characteristic magnetic signal.

The controlling computer stores the recorded characteristic magnetic signal of paclitaxel. It transmits the data and the corresponding sampling rate information to the waveform generator. Accordingly, the waveform generator may generate the electronic signal of the defined waveform from the controlling computer. Then, the subsequent wide band amplifier ensures that the electronic signal from the waveform generator has been appropriately amplified to be able to drive the subsequent load, which is the Helmholtz coil. The Helmholtz coil transforms the received electronic signal into the corresponding magnetic energy and emits it to the tissue culture dish that contains glioma cells, which is placed in the center region of the Helmholtz coil. The emitted magnetic intensity in the center region of the Helmholtz coil is designed to be at the level of 1 mT. The degree of homogeneity of 1% corresponds to the center region of the Helmholtz coil with a size of 90 mm $\times$ 60 mm $\times$ 20 mm. When the current in the Helmholtz coil is 20 A, the magnetic intensity of the center region of the Helmholtz coil is 1.10 ± 0.01 mT.

2.6. Cell culture and exposure groups

U87 cells purchased from the Chinese Academy of Sciences were cultured in T25 culture dishes (Thermo Fisher Scientific, USA) at a cell density of 4 $\times$ 10⁴ cells/ml in Dulbecco's modified Eagle's medium (DMEM, Invitrogen Inc. Gibco BRL, Gaithersburg, MD, USA) supplemented with 10% fetal bovine serum (Gibco, Invitrogen, Carlsbad, CA, USA) at 37 ± 0.5 °C in a humidified atmosphere with 5% CO₂. Cell cultures with 80% confluence were routinely trypsinized and split at 1:3. Groups of 4 $\times$ 10⁴ cells underwent (1) no treatment, (2) exposure to CMSP (or MSC) alone, (3) treatment with 5 μM paclitaxel (PTX) alone, or (4) a combination of PTX and CMSP (or MSC) treatments for 12 h or 24 h. Morphological and biochemical investigations were performed after each treatment.

2.7. Cell viability assay

Cell viability was measured in duplicate samples with a cell counting kit 8 (CCK-8) in 4 independent experiments. U87 cells were seeded in 96-well plates at a density of 2 $\times$ 10³ cells per well, placed back into the incubator for incubation for 24 h, cultured for 12 h or 24 h before the addition of 10 μL of CCK-8 reagent to each well, and incubated for another 2 h. The absorbance at a wavelength of 450 nm was detected with a microplate reader (Thermo Fisher Scientific).

2.8. Cell cycle analysis by flow cytometry

The PI staining method was used to detect the cell cycle distribution. Briefly, the cells were washed three times with PBS, resuspended by adding precooled 70% ethanol, and then stored in the refrigerator at −20 °C. The cells were washed with PBS, PI staining solution was added, and the cells were incubated at room temperature for 30 min before flow cytometry detection. Finally, the distribution of the cell cycle was analyzed by FlowJo software.

An inverted phase-contrast microscope was used to investigate morphological cellular changes after 12 h and 24 h, which were recorded by a Digital Sight camera system (Model eclipse Ts2, Nikon, Tokyo, Japan). The results presented in our study are from cell experiments repeated at least 3 times. Cell data were analyzed with GraphPad Prism 7.

3. Experimental results

3.1. Experiments for the inhibition of glioma cells

All experiments were carried out in a magnetically shielded room. The CMSP and the corresponding MSC were detected and recorded based on the grid search algorithm [12] to explore the SR parameter combinations for the established SQUID system. The optimal SR parameters of the stimulating stochastic magnetic noise magnitude and the bias magnetic field were 50 nT and 0 nT, respectively, for the established SQUID system. Fig. 3 illustrates the details of the obtained signals for which the characteristic magnetic signal of paclitaxel was effectively enhanced by the SR method.

Fig. 3.

The signals (CMSP and MSC) obtained by the detection system for the characteristic magnetic signal of paclitaxel.

According to direct observation, paclitaxel's characteristic magnetic signal has three different components at frequencies of 13 kHz, 18 kHz and 24 kHz compared with the control signal. It should be clearly denoted here that it cannot be definitively determined whether these spectral differences come from the characteristic magnetic signal of paclitaxel. This is the first demonstration of the details of paclitaxel's characteristic magnetic signal. The theoretical proof and identification of the spectral details of this signal is an important future research direction for our team. A set of comparisons of the detected magnetic field signals of paclitaxel before and after the optimization of the SR parameters is provided in Fig. 4. It can be seen that the optimal SR parameter may effectively improve the signal detection of SQUID for the weak characteristic magnetic signal of paclitaxel.

Fig. 4.

A set of comparisons of the detected magnetic field signals of paclitaxel before and after the optimization of the SR parameters. (a) was obtained with the optimal SR parameter. (b) and (c) were obtained before the optimization of SR parameters.

By utilizing the electronic system emitting the magnetic energy, we first applied the CMSP signal to the glioma cells. The signals were amplified by 24 dB with the wide-band amplifier before entering the Helmholtz coil. Cell viability was evaluated after 12 and 24 h by CCK8 assay. The results are shown in Fig. 5. The paired-sample t-test is applied to calculate the p values for the experimental results of different settings. Statistical significance was observed.

Fig. 5.

The cell viability experimental results by applying the paclitaxel signal. (a) and (b) are the results after 12 and 24 h, respectively. CMSP denotes the use of the obtained characteristic magnetic signal of paclitaxel. PTX denotes the use of paclitaxel.

It can be seen that the magnetic energy emitted based on the recorded paclitaxel signal achieves an effect that is equal to (or even slightly better than) that of the drug paclitaxel. The effectiveness of the detected paclitaxel characteristic magnetic signal for the inhibition of glioma cells was clearly demonstrated. We also simultaneously applied both the magnetic energy of the characteristic magnetic signal of paclitaxel and the paclitaxel drug to one set of glioma cells. It can be observed in Fig. 5 that the inhibitory effect of this treatment on glioma cells was better than the effect of using the magnetic energy or the paclitaxel drug individually. The magnetic energy of the signal appears to enhance the inhibitory effect of paclitaxel. This phenomenon might indicate that the magnetic signal is the intrinsic reason that paclitaxel can impact the proliferation of cancer cells. The impact of the additional characteristic magnetic signal of paclitaxel is equivalent to increasing the drug concentration of paclitaxel, which improves the inhibitory effect on glioma cells.

For comparison, we also performed the experiments with the same settings as above but replacing the CMSP signal with its corresponding control signal as MSC. The results are shown in Fig. 6. The applied magnetic energy of the control signal had almost no effect on the inhibition of glioma cells according to cell viability, and statistical significance was not observed. This finding indicates that the inhibitory effect on glioma cells was caused by the magnetic energy of paclitaxel's characteristic magnetic signal. General magnetic energy does not effectively cause this inhibitory effect.

Fig. 6.

The experimental results with the corresponding control signal (MSC). The settings are the same with the one for Fig. 5 but only by replacing the paclitaxel magnetic signal (CMSP) with its corresponding control signal (MSC). (a) and (b) are the results after 12 and 24 h, respectively.

3.2. CMSP induced morphological changes in U87 cells and inhibited cell proliferation through apoptosis

Furthermore, morphological changes, such as soma size and shape, were assessed and recorded after 24 h (shown in Fig. 7). Exposure to CMSP induced significant morphological changes in U87 cells, mainly including processes and soma alterations, increased cell surface area, especially elongation or shortening of the processes, shrinkage/swelling of the soma and apoptotic-like cell morphologies (surface blebs, pyknotic nucleus). Exposure to CMSP also increased the number of PTX-induced apoptotic cells, as shown in Fig. 7b.

Fig. 7.

Morphology of U87 cells exposed to different treatments for 24 h. (a) U87 cells of the control group and other groups are shown 24 h later under a 40 $\times$ light microscope. (b) View under a 100 $\times$ light microscope of the morphological changes in U87 cells exposed to CMSP, mainly including processes and soma alteration, increased cell surface, especially elongation or shortening of the processes, shrinkage/swelling of the soma and apoptotic-like cell morphologies (surface blebs, pyknotic nucleus). Bars: 100 µm.

Morphological changes were observed in U87 cells after CMSP treatment for 24 h (Fig. 7). CMSP-treated U87 cells showed significant process elongation or shortening and soma shrinkage or swelling, which was similar to the effects on cells treated with PTX. Moreover, cells presented with apoptotic-like changes (surface blebs, pyknotic nucleus) when CMSP treatment was performed. Furthermore, exposure to CMSP facilitated PTX-induced cell apoptosis, resulting in cell proliferation inhibition.

3.3. CMSP promoted the accumulation of G2-M in the cell cycle, inhibiting cell proliferation

In addition to the monitoring of cell apoptosis induction, flow cytometry analysis was performed to evaluate the biological effect of CMSP on U87 cells. After 24 h of treatment with CMSP, cell cycle blockade was observed in tumor cells at G2 phase (Fig. 8). The number of tumor cells in G1, G2, and S phase was 58.87%, 4.32% and 36.82%, respectively, without CMSP treatment (control group). The number of cells treated with CMSP was 54.67%, 7.6% and 37.73%, respectively. Tumor cells in G2 phase presented a greater increase in the CMSP group than in the control group. It was hypothesized that the accumulation of tumor cells in G2 phase might cause cell apoptosis and inhibit proliferation.

Fig. 8.

CMSP promoted the accumulation of G2-M in the cell cycle, resulting in the inhibition of cell proliferation. Representative histogram of flow cytometry-based cell cycle analysis with/without CMSP.

4. Discussion

In our study, we proposed a systematic approach for the detection of the extremely weak magnetic signal generated from paclitaxel. The drug itself is commonly considered to be neutral. However, our study confirmed the existence of its characteristic magnetic signal, and the details of the detected signal have been clearly and quantitatively presented for the first time in the manuscript. The principal mechanism for the existence of this characteristic magnetic signal still needs to be further studied. The reason that this characteristic magnetic signal exists might be due to the solution used to load the drug. Some relevant studies in water science have shown that there is a strong hydronium-π interaction between hydronium ions in solution and the surface of aromatic rings rich in π electrons, making biomolecules that contain aromatic rings magnetically responsive [13,14]. Most drug molecules have aromatic ring structures, which, according to the above findings, is an indirectly plausible basis for the generation of magnetic fields by aqueous solutions of antitumor drugs. Although the observation of such a signal in the currently applied solution system is stable, we plan the systematic testing of other solution systems to obtain further evidence for the study of the unknown mechanism. Our study tried to pave the way for related research with the proposed systematic approach.

Some studies have shown that magnetic fields are an effective form of physical oncology therapy, but the parameters of these magnetic fields were determined by trial-and-error without clear guidelines or mechanism explanations [15,16,17,18]. Among these studies, refs. [15,16] are reports of magnetic fields in the treatment of gliomas, while refs. [17,18] are the reports of extracranial tumors. Although these references demonstrated the effectiveness of magnetic field therapy to some extent, a wide range of magnetic field frequencies (10 Hz-21 kHz) were reported, with varying benefits for tumor treatment. Although the evidence provided by these studies is not directly related to the present study, they provide a basis for the present study. It would certainly be a major breakthrough for the magnetic field therapy of tumors if there is a way to find the optimal parameters for tumor magnetic field therapy. The proposed approach of our study is to provide such clues through the detection of weak characteristic magnetic field signals from drugs. Our experiments clearly detected the characteristic magnetic field signal of paclitaxel by SQUID. This magnetic signal has an inhibitory effect on the proliferation of glioma U87 cells similar to that of paclitaxel.

It should be noted that PI staining and CCK-8 in the current study were used for the cell viability assay. However, these methods cannot distinguish early or late apoptotic cells from the Sub-G1 group. We will include Annexin V-FITC/PI FACs in our experiments in the future to investigate whether this method can clearly demonstrate inhibitory effects, which may make the related experimental results even more convincing. Moreover, it should be noted that the in vivo environment of glioma is more complicated than the in vitro environment. Many treatments function well in vitro experiments but have no effects in vivo experiments. To further investigate the fundamental hypothesis in our study, in vivo experiments are planned in the near future. In our study, cell proliferation was significantly inhibited after treatment. However, cell proliferation is only one among many meaningful biological criteria. For our future studies, more biological characteristics of malignant cells will be investigated, such as cell migration, invasion, and tumorigenesis.

The detection of the characteristic magnetic signal is based on the identification of the difference between the data from signal and control samples. According to our study, this difference is extremely subtle and difficult to detect. To achieve effective signal detection, the SR method is essential. The extent of the stimulated SR phenomenon is based on the appropriate selection of the adjustable parameters of the detecting system. However, the search space of the adjustable parameters is quite large, and it is impossible to search the parameter space effectively without the utilization of computerized algorithms. From the above points of view, the introduction of the artificial intelligence (AI) method for work on this topic is necessary and straightforward. The AI method is capable of detecting slight variations in data and effectively searching the parameter space [12]. Further exploration of the utilization of the AI method is one of our future research plans.

In our study, we applied the energy of the characteristic magnetic signal to glioma cells, and the inhibitory effect was demonstrated to be as clear as that of paclitaxel. This might provide an ideal treatment direction for glioma patients or even all cancer patients. The treatment method using the characteristic magnetic signal itself has almost no drug-related side effects at all. The magnetic energy field of the characteristic magnetic signal simulates the efficacy of drugs and has no penetration problem. For glioma, the blood‒brain barrier will not impact this magnetic treatment. Moreover, the magnetic energy can be easily controlled and focused on the tumor region without impacting other normal tissue. If we can detect a variety of drug signals (not just paclitaxel) related to glioma treatment [19], we can implement simultaneous multitarget magnetic therapy for glioma, and theoretically, we can truly achieve the maximum-safe-target-therapy in clinical practice for the first time. All of these factors make research of on the characteristic magnetic signals of drugs both promising and meaningful for the overall health of entire human beings.

5. Conclusion

To explore a novel treatment method for glioma, we hypothesized that a chemical substance or biological agent may generate a characteristic magnetic signal, which is the fundamental reason that the chemical substance or biological agent works for cancer treatment. Based on this hypothesis, a SQUID device using the SR method was established, and the characteristic magnetic signal of paclitaxel was detected and clearly visualized. The cell experimental results demonstrated that the detected characteristic magnetic signal of paclitaxel had effectiveness equivalent to that of paclitaxel for the inhibition of glioma cells. Our study indicates that paclitaxel's characteristic magnetic signal might be utilized as an ideal treatment method for glioma patients due to its lack of side effects, high focusable penetration and effectiveness.

Declaration of competing interest

The authors declare that they have no conflicts of interest in this work.

Biographies

Jinhua Yu(BRID: 09872.00.18087) received the Ph.D. degree in Electronic Engineering Department of Fudan University, Shanghai, China, in 2008. From 2008 to 2010, she was a postdoctoral fellow with the Department of Bioengineering, University of Missouri, Columbia, MO. She is currently a full professor in Biomedical Engineering Center of Fudan University. Her current research interests include medical image/signal analysis, radiomics, and deep learning in medical applications.

Liangfu Zhou(BRID: 08925.00.93935) received B.S. degree from Shanghai First Medical College in 1965 and has been teaching there ever since. He was elected as an academician of the Chinese Academy of Engineering in 2009. He has long been engaged in the microinvasive neurosurgery and basic research work of neuroscience. He was awarded Second Prize of National Science and Technology Progress (NSTP) for three times and Third Prize of NSTP for two times. In 2012, he was honored as Man of the Year by WFNS with granted Outstanding Achievement Award. He has published more than 400 academic papers and 7 books.