Team:ZJU-China/Description

• Inspiration
• Background
• Existing Methods
• Our Solution
• Future
• References

• Home
• Team
  • Members
  • Attributions
  • Medals
• Project
  • Description
  • Background
  • Design
  • Magnetosome
  • Experiments
  • Results
  • Future
• Model
  • Model
  • Engineering
  • Proof of Concept
• Parts
  • Contribution
  • Improve
  • New Parts
• Human
  • Human Practices
  • Education
  • Collaborations
  • Partnership
  • Safety
  • Implementation
  • Entrepreneurship

Description

Inspiration

“Prajna Paramita, soon as soon as
life be beautiful like summer flowers and death like autumn leaves
Also care about what has”

This is a poem Jiamin Zhang read on a TV program called The Reader. It comes from Tagore's collection of poems called Stray Birds.

Behind the poem is her nearly three decades battle with breast cancer, back and forth. In an interview with the show, she told us how she went from a breast cancer patient to a breast cancer rehabilitation volunteer.

Here's a picture of her on the show, with a pink ribbon on her chest (Figure 1).

Figure 1. Zhang Jiamin in the TV program, The Reader.

Not only had she experienced breast cancer herself, but she cared about the entire population of breast cancer patients. She found that many breast cancer patients faced physical disability and great pain from fear of recurrence. Therefore, she opened a 24-hour hotline for breast cancer patients and helped them nearly 10,000 times in more than 20 years, bringing courage and hope to many people.

We were deeply moved when she said that she hoped that "Chinese women would not be plagued by breast cancer any more", so we hope to carry forward this belief and make some contributions to breast cancer patients in China by applying synthetic biology methods.

Background

Despite important advances in research, breast cancer remains a major health problem and represents a top biomedical research priority. The incidence of this aggressive disease with approximately 17,000,000 new cases each year remains alarmingly high^[1].

According to the International Agency for Research on Cancer (IARC), breast cancer had the highest incidence and death rates of all cancer types globally in 2018, including women and men. As the graph shows below, the incidence of breast cancer is much higher than that of prostate cancer, the second most common (Figure 2).

Figure 2. Estimated age-standardized incidence rates (World) in 2018, worldwide, both sexes, all ages.

The problem of breast cancer in China is also not optimistic, accounting for 12.1% of new cases and 9.6% of deaths worldwide, respectively.

In the face of these problems, accurate screening is of great significance and can greatly improve survival rate. The current methods mainly include clinical examination, imaging examination and surgical biopsy.

Existing Methods

Procedures commonly used in breast-cancer diagnosis are mammography, ultrasonography, MRI, and PET. However, physical examination remains important because a certain proportion (11%) of breast cancers are not seen on mammography^[2].

Compared with other methods, MRI has many advantages, such as high resolution and multi-sequence imaging, which is determined by the basic principles of imaging.

Mediolateral oblique view from a screening mammogram in a 54-year-old woman shows a small cluster of microcalcifications in the upper outer quadrant of the right breast^[3]. A detailed spot magnification view is given in Figure 3.

Figure 3. Mediolateral oblique view from a screening mammogram in a 54-year-old woman.

MRI contrast agents typically function by detectably altering the longitudinal (T1) or transverse (T2) relaxation times of nearby hydrogen nuclei^[4]. Gadolinium-based contrast agent, a sort of T1 contrast agent, has been widely used for MRI. However, gadolinium is not always desired due to its inherent enhancement properties and potential side effects (e.g. nephrogenic systemic fibrosis)^[5]. Therefore, it is imperative to develop the ideal contrast agent that meet the demand of both contrast effect and clinical safety.

Our Solution

Now there is no specific MRI contrast agent, so we have MagHER2some.

Magnetosomes with high saturation magnetization and good biocompatibility have shown potential values as MRI contrast agents^[6]. Our project focuses on HER2-positive breast cancer by modifying the magnetosome using protein-display technology to create a contrast agent that targets HER2-positive breast cancer cells for MRI, MagHER2some.

Figure 4. A schematic design of our project.

To better target HER2, we use single-chain variable fragment (scFv) as our weapon. As shown in Figure 4, scFv-Fc fusion protein was expressed in a kind of E.coli, SHuffle^® strains, and magnetosomes containing ZZ protein on the membrane surface were generated in magnetotactic bacteria.

Then the next step was to connect scFv on the surface of magnetosomes through the interaction between Fc and ZZ in vitro, so as to target HER2-positive breast cancer cells. In the successful targeting of HER2-positive breast cancer cells, MagHER2some will act as an excellent contrast agent, playing the role of enhanced MRI.

Visit the Design page to learn more details.

Future

If we can successfully target breast cancer cells, then we can go a step further and build a platform that can detect multiple diseases.

If we can find targets for other diseases and corresponding scFv, we only need to change the scFv in our project, and other structures like mamC and Fc have no need to be changed.

Looking forward to the future, we aim to develop a versatile targeted imaging platform apply to the clinical diagnosis of more types of tumors.

In addition, if MagHER2some can successfully target breast cancer cells, we have ambitions to make it do more than just imaging: magnetic hyperthermia.

MagHER2somes have the right size and are superparamagnetic, which would be an excellent material for magnetic hyperthermia.

And with the characteristic of precise targeting, our magnetic body can reduce the damage to normal tissues in magnetic hyperthermia, so it can perfectly realize the integration of diagnosis and treatment in the future.

Visit the Future page to learn more details.

References

[1]. DeSantis, C., Ma, J., Bryan, L., & Jemal, A. (2014). Breast cancer statistics, 2013. CA: a cancer journal for clinicians, 64(1), 52–62. https://doi.org/10.3322/caac.21203

[2]. Benson, S. R., Blue, J., Judd, K., & Harman, J. E. (2004). Ultrasound is now better than mammography for the detection of invasive breast cancer. American journal of surgery, 188(4), 381–385. https://doi.org/10.1016/j.amjsurg.2004.06.032

[3]. Mann, R. M., Cho, N., & Moy, L. (2019). Breast MRI: State of the Art. Radiology, 292(3), 520–536. https://doi.org/10.1148/radiol.2019182947

[4]. Zhang, F., Li, F., Lu, G. H., Nie, W., Zhang, L., Lv, Y., Bao, W., Gao, X., Wei, W., Pu, K., & Xie, H. Y. (2019). Engineering Magnetosomes for Ferroptosis/Immunomodulation Synergism in Cancer. ACS nano, 13(5), 5662–5673. https://doi.org/10.1021/acsnano.9b00892

[5]. Wesolowski, J. R., & Kaiser, A. (2016). Alternatives to GBCA: Are We There Yet?. Topics in magnetic resonance imaging : TMRI, 25(4), 171–175. https://doi.org/10.1097/RMR.0000000000000096

[6]. Zhang, Y., Ni, Q., Xu, C., Wan, B., Geng, Y., Zheng, G., Yang, Z., Tao, J., Zhao, Y., Wen, J., Zhang, J., Wang, S., Tang, Y., Li, Y., Zhang, Q., Liu, L., Teng, Z., & Lu, G. (2019). Smart Bacterial Magnetic Nanoparticles for Tumor-Targeting Magnetic Resonance Imaging of HER2-Positive Breast Cancers. ACS applied materials & interfaces, 11(4), 3654–3665. https://doi.org/10.1021/acsami.8b15838

aannnaaaaannnnnnnnnnnnn

aannnnnnnnn