Human Practices

Overview

Our project aims to develop a biological method for iron oxide nanoparticles to be used in targeted therapy for cancer. We have conducted extensive research, consulted experts, and implemented human practices to ensure the safety, efficiency, and accessibility of our proposed solution. the safety, efficacy, and accessibility of our proposed solution. Throughout the engineering cycle of our project, we have collaborated with medical professionals specializing in oncology, radiotherapy, and surgery. In addition to consulting medical professionals, we have interviewed experts in the fields of nanotechnology, synthetic biology, protein engineering, and ferroptosis. Their expertise has been instrumental in design and optimize our biosynthesis method for iron oxide nanoparticles, ensuring scalability, reproducibility, and cost-effectiveness. The central theme in our project has is safety. We are fully aware that many existing cancer therapies, such A central theme in our project has been safety. We are fully aware that many existing cancer therapies, such as chemotherapy, have significant side effects. For example, it is reported that 46.3% of breast cancer patients who undergo chemotherapy have experienced the side effects of chemotherapy. patients who undergo chemotherapy experience side effects. Additionally, we have actively engaged with stakeholders, including patient advocacy groups, healthcare providers, and pharmaceutical companies, to gather insights and address concerns related to safety. An overview of our human practices and how they shaped our project is described below:

Offline sharing in CCiC.

Fig1: Integrating Feedback into Design

Offline presentation in CCiC.

Fig2: Integrating Feedback into Safety Considerations and Proposed Implementation

Nanoparticle Separation

Interviewee

Screenshot of the Wall of Wonder.

Bobo DANG


School of Life Sciences

Biology
Laboratory of Protein Engineering and Protein Therapeutics

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Looking for

We contacted him due to his extensive expertise in protein design and biopresentation technology, and we are seeking his guidance on the feasibility of implementing protein-coupled nanoparticles in PEG and achieving direct conjugation in prokaryotic organisms.

Question we asked

  1. When isolating and synthesizing iron oxide nanoparticles from E. coli, we encountered the need to remove a significant amount of biomaterial. Could you please recommend an effective washing agent that can achieve good removal results without significantly damaging the surface composition of the iron oxide nanoparticles?
  2. How can we achieve the coupling between antibodies and the surface of iron oxide nanoparticles? We are considering two approaches: direct coupling to the isolated iron oxide nanoparticles, where the surface coating component may be phospholipids, and pre-coating the nanoparticles with a layer of PEG (polyethylene glycol) before coupling. Do you have any suggestions for the design of coupling components? We have thought about the Spytag/Spycatcher system.
  3. Is it possible to enhance the connection between the tail end of the antibodies and the nanoparticles through a biocompatible method of modifying the binding site?
  4. After synthesizing our antibodies, we aim to improve their targeting efficiency. Are there any biocompatible methods available to modify the binding site at the head end of the antibodies?

Takeaways

  1. During our discussion on the self-assembly of bio-synthetic nanoparticles and antibodies in Escherichia coli, professor Dang expressed concerns regarding the stability of the vesicles on the surface of the nanoparticles compared to the bacterial membrane. Professor Dang suggested that this instability might lead to the destruction of the nanoparticle structure when separating them with antibodies. Consequently, he proposed that it would be more feasible for us to synthesize and assemble the components separately.
  2. Another topic of our discussion was elution during the separation of nanoparticles. professor Dang suggested that we could employ organic solvents for washing and filtration. Additionally, considering the necessity of a layer of PEG membrane, professor Dang recommended attempting to dissolve PEG in organic solvents to achieve the desired replacement.
  3. Professor Dang opined that the surface composition of the nanoparticles is not necessarily crucial. As long as the final objective of antibody connectivity is achieved, the existence of amino and carboxyl groups on the surface of bio-synthesized nanoparticles should facilitate connection. Professor Dang also proposed that the possibility of employing harsh solvents to wash the nanoparticles and observe their binding behavior with antibodies.
  4. In relation to connecting the antibodies and nanoparticles, professor Dang mentioned the utilization of EDC (1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide).
  5. Overall, an additional point to consider is that using PEG coating might not be meaningful. Commercially available chemically-synthesized nanoparticles are already coated with PEG. Therefore, the coating on the surface of bio-synthesized nanoparticles lacks significance.

Interviewee

Professor Hongyu CHEN

Hongyu CHEN


School of Science
School of Engineering (Affiliated)

Chemistry
Materials Science and Engineering
Laboratory of Nanosynthesis

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Looking for

As a specialist in chemical synthesis and nanoparticle applications, we are keen to learning from Professor Chen about common synthesis and separation methods, seeking his guidance and feedback for brainstorming, and enhanceing our knowledge of iron oxide nanoparticles and their market applications.

Question we asked

  1. We would like to understand the current methods for chemically synthesizing iron oxide nanoparticles in the laboratory.
  2. Is biologically synthesizing nanoparticles feasible?
  3. Does our proposed plan meet the requirements of scientific research, and does it exhibit sufficient innovation?
  4. What are the common methods for characterizing nanoparticles in a chemical laboratory?
  5. In general chemical laboratories, is centrifugation the typical method for nanoparticle separation? Does it work for nanoparticles of different diameter sizes?

Takeaways

  1. Professor Chen's laboratory typically employs a method involving the thermal reduction of a reductant to prepare nanoparticles, followed by ligand exchange to obtain stable products.
  2. Chemical synthesis can now achieve a relatively narrow size distribution of iron nanoparticles by controlling reaction conditions.
  3. Typically, nanoparticles can be separated by sedimentation using centrifugation. Professor Chen's laboratory generally synthesizes particles with diameters in the tens of nanometers range, which are suitable for centrifugation separation. However, for smaller nanoparticles, the difficulty of sedimentation significantly increases. For nanoparticles with a diameter of around 10 nm, it may require centrifugation at over 100,000 x g to achieve efficient separation.
  4. We learned from Professor Chen that TEM is commonly used for characterizing iron oxide nanoparticles.
  5. Biologically synthesizing nanoparticles is feasible, and Professor Chen recommended several researchers from the Chinese Academy of Sciences Institute of Geology and relevant academic conferences on geomagnetic biology to us.

Interviewee

Professor Hongfei WANG

Jiawei LIU


Institute of Geology and Geophysics, Chinese Academy of Sciences

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We are interested in understanding the research efforts related to the coating components of biologically synthesized magnetic nanoparticles and how we can identify these components. We also want to know if there are established strategies to separate the magnetic nanoparticles from organelles or biomolecules of similar size in biological synthesis. Additionally, we are curious about the impact of incomplete separation on nanoparticle characterization, particularly whether dynamic light scattering would yield inaccurate results in this scenario. Lastly, we are seeking information about alternative characterization techniques that may be more suitable.

Question we asked

  1. Are there any research efforts focused on determining the coating components of biologically synthesized magnetic nanoparticles? Is there a way to identify the coating components?
  2. Regarding the synthesis of magnetic nanoparticles through biological methods, are there any well-established separation strategies available to separate the magnetic nanoparticles from organelles or biomolecules of similar size?
  3. If complete separation is challenging, would it have a significant impact on the characterization of the nanoparticles? For example, would dynamic light scattering yield inaccurate results in this case? If so, are there more suitable characterization techniques available?

Protein analysis and decomposition

  1. The professor said that it may be necessary to detect and identify proteins, including chemical bond composition and three-dimensional structure analysis, and to understand some mechanisms of the biosynthetic nanoparticle process so that we can make better prediction and identification.
  2. We firstly doubted that we couldn't use the ultrafilteration due to the low spinning speed and the content may jam the device. However, after comparing Hemodialysis, Centrifugation, Chromatography and Ultrafiltration, Prof. Liu still suggested the last one. That's because ultrafiltration won't agglomerate the protein and He encouraged us to try various experiment methods since we can not ensure every step is correct in our procedure. As long as we have an idea, there is no need to worry about the failure.
  3. For this problem, incomplete separation can affect the physical and chemical data characterization of nanoparticle products, but for biocompatibility characterization such as cytotoxicity testing, unisolated substances usually do not have much impact, because other cell debris and metabolites usually do not affect the normal growth and differentiation of cells.

General Synthetic Biology

Interviewee

Screenshot of the Wall of Wonder.

Kechun ZHANG


School of Engineering

Materials Science and Engineering
Laboratory of Biomanufacturing and New Materials

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Looking for

We seek information and recommendations on E. coli culture, antibody synthesis, and conjugation of iron oxide nanoparticles (IONPs) with antibodies. Specifically, we want to know about culturing E. coli in SOB protein medium, synthesizing antibodies in E. coli without improper double sulfur bond formation, and conjugating IONPs with antibodies like Au NPs. Additionally, we seek guidance on optimizing IONP conditions, developing an AI model for nanoparticle-protein interactions, and addressing challenges in mass production.

Question we asked

  1. Can E. coli be cultured in SOB (Super Optimal Broth) protein medium?
  2. Is it possible for antibodies to be synthesized in E. coli without the formation of double sulfur bonds at the wrong location?
  3. Can iron oxide nanoparticles (IONPs) be conjugated with antibodies, similar to how gold nanoparticles (Au NPs) and antibodies form an Au-S bond?
  4. What should be prioritized when conducting tests with iron oxide nanoparticles, and how can we optimize the conditions for the best product?
  5. Is it feasible to construct an AI model to predict interactions between nanoparticles and proteins, considering the limited experimental data available in this field?
  6. What are the challenges and considerations involved in the mass production of iron oxide nanoparticles, such as comparing biosynthesis's yield with , reaction time, reactant inhomogeneity with chemicalsynthesis's, and controlling particle size?

Takeaways

  1. We discussed culture medium proteins for E.coli, such as SOB (Super Optimal Broth) protein.
  2. The synthesis of antibodies in E.coli was also addressed. Dr. Zhang pointed out that even when using strains with partially blocked reduction pathways, there is a possibility of the double sulfur bond of the antibody forming at the wrong location. To confirm this, we referred to Ahmadzadeh et al. (2020), where it was found that our desired antibody can indeed be synthesized in E.coli.
  3. The conjugation of iron oxide nanoparticles (IONPs) and antibodies was another topic of our discussion. Dr. Zhang mentioned that previous research has shown that Au nanoparticles and antibodies can form the Au-S bond. However, there is no information available regarding whether this method works for iron oxide nanoparticles. Currently, we are working on this issue and drawing inspiration from Lee et al. (2021), who proposed the use of the SpyTag/SpyCatcher system for conjugation.
  4. Dr. Zhang advised us to pay attention to our schedule, as we will be conducting tests to validate our hypothesis. He suggested optimizing the conditions for producing the best product with iron oxide nanoparticles as a priority.
  5. We also inquired about the possibility of constructing an AI model to predict interactions between nanoparticles and proteins. However, Dr. Zhang pointed out that the limited amount of experimental data available in this field and the scarcity of published data make it necessary to postpone this plan. Perhaps in the future, when we gather more data, we will be able to proceed with this project.
  6. Lastly, we discussed the mass production of IONPs. Dr. Zhang emphasized the need to compare the biosynthesis yield with chemicalsynthesis. Additionally, mass production involves considerations such as reaction time and the inhomogeneity of reactants in a large reactor. Moreover, controlling the particle size of iron oxide nanoparticles poses a challenge.

Nanoparticle Application

Interviewee

Dr. ZHOU

Yaofeng ZHOU


School of Engineering

Cheng Research group

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Looking for

Darko et al. (2022) compiled a list of 344 non-redundant abbreviations from reptile species descriptions. Oliveira et al. (2022) found that prone positioning in nonintubated individuals with COVID-19 improved outcomes. Rai et al. (2017) demonstrated the feasibility of using text-message surveys for real-time data collection in low-income clinic populations. Abdo (2021) discussed the use of simplified molecular input line system (SMILES) representation for molecular similarity searching, while Albrechtová et al. (2019) outlined procedures for quantifying plant structures using image analysis.

Question we asked

  1. Can anaerobic bacteria be directly used for target therapy, as proposed in the study by Ouajdi Felfoul et al. (2016)?
  2. What are the potential limitations of our target therapy, specifically in relation to the formation of a protein corona around nanoparticles coated with antibodies?
  3. Are there any specific methods or techniques for the conjugation of antibodies and nanoparticles that we should refer to? (Referring to the Advanced Materials review and the work of Professor Zhang Xianzheng)
  4. How can we ensure the specificity of the antibody-nanoparticle conjugation and prevent the functional domain of the antibody from binding to the nanoparticles?
  5. What is the impact of Extracellular Polymeric Substances (EPS) on the functionality of nanoparticles, and are there any studies that have investigated this?
  6. What methods can be used to measure the interaction kinetics and affinity between biomolecules, specifically in relation to antibody-antigen interactions in target therapy?
  7. What techniques can be used for the separation of nanoparticles from E. coli, considering that PD-10 is only suitable for the elution of ferric chloride?

Takeaways

  1. In terms of target therapy, Dr. ZHOU discussed a study by Ouajdi Felfoul et al. (2016) that proposes a novel approach involving the direct use of anaerobic bacteria for target therapy.
  2. ZHOU also addressed the potential limitations of our target therapy. When nanoparticles coated with antibodies are introduced into the human body, they tend to attract numerous proteins, resulting in the formation of a protein corona around the nanoparticles. This protein corona can significantly affect the nanoparticles' biological behavior and fate.
  3. In regards to antibody-nanoparticle conjugation, Dr. ZHOU recommended referring to a review in Advanced Materials (Antibody Conjugation of Nanoparticles as Therapeutics for Breast Cancer Treatment, Int. J. Mol. Sci., 2020), which discusses various methods for antibody-nanoparticle conjugation. This review greatly expanded our understanding of conjugation techniques.
  4. Dr. ZHOU also highlighted the work of Professor Zhang Xianzheng in the field of conjugation, which is highly relevant to our research topic.
  5. Dr. ZHOU emphasized the importance of ensuring the specificity of the conjugation, in order to prevent the antibody's functional domain from binding to the nanoparticles. He recommended modifying the antibody's tail through PEGylation or the use of a branched tail, as well as considering the use of a secondary antibody to address this issue.
  6. Dr. ZHOU also mentioned the potential interference posed by Extracellular Polymeric Substances (EPS) on the functionality of nanoparticles. Subsequently, we discovered a study by Gao et al. (2019) that investigated the adsorption of EPS from E. coli onto titanium dioxide nanoparticles (nTiO), demonstrating that EPS effectively reduced the concentration of nTiO in the solution. Furthermore, a study by Wang et al. (2016) found that EPS produced by E. coli could sequester nanoparticles, thereby diminishing their bactericidal activity.
  7. To measure the interaction kinetics and affinity between biomolecules, Dr. ZHOU recommended employing Bio-Layer Interferometry (BLI), which enables the detection of antibody-antigen interactions in target therapy.
  8. Regarding to the separation of nanoparticles from E. coli, Dr. ZHOU discussed the use of PD-10. However, we later discovered that this technique is only suitable for the elution of ferric chloride.

Ferroptosis of Iron Oxide Nanoparticle

Interviewee

Screenshot of the Wall of Wonder.

Yilong ZOU


School of Life Sciences

Biology
The Laboratory of Functional Lipidomics and Metabolic Regulation

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We seek guidance on coupling antibodies to iron oxide nanoparticles, considering direct coupling or coupling with a PEG layer. Specifically, we ask for suggestions on protein design using the Spytag/Spycatcher system. Additionally, we inquire about the sensitivity of breast cancer cells to ferroptosis and the potential of our synthesized iron oxide nanoparticles to induce apoptosis in these cells. Our questions focus on optimizing antibody coupling, understanding the effects of nanoparticles on breast cancer cells, and their potential to induce apoptosis.

Question we asked

  1. We currently have two approaches for coupling antibodies to the surface of iron oxide nanoparticles. The first approach involves direct coupling with isolated iron oxide nanoparticles, where the surface coating component could be phospholipids. The second approach involves first forming a layer of polyethylene glycol (PEG) on the surface, followed by coupling with PEG. Do you have any suggestions for protein design for coupling? We have considered the Spytag/Spycatcher system. Also, do you think breast cancer cells are highly sensitive to ferroptosis?
  2. Do you think our synthesized iron oxide nanoparticles can induce apoptosis in breast cancer cells after entering them?
  3. Do you think our synthesized iron oxide nanoparticles can induce apoptosis in breast cancer cells after entering them?

Takeaways

  1. Dr. Zou emphasizes the catalytic role of ferrous ions (Fe2+) in ferroptosis and suggests that conducting experiments to validate the functional similarities of our iron oxide nanoparticles (IONPs) is necessary.
  2. Additionally, he asserts that IONPs can serve as a sustained-release agent for iron ions, which he views as a significant advantage in our project.
  3. Furthermore, Dr. Zou raises the important concern of considering the components of the coating applied to the IONPs, as certain toxic substances have the potential to elicit an immune response in vivo.
  4. Regarding to the experimental design, he suggests adhering to the hierarchy principle and conducting a feasibility study before proceeding with formal experiments.
  5. He proposes a definition of synthetic biology as the manipulation of gene editing to link together more than three proteins. In light of this definition, he contends that our project does not substantially fall under the category of synthetic biology and emphasizes the need to present relevant data to enhance its competitiveness.
  6. Dr. Zou also highlights that antibodies operate within a non-cell-autonomous context. This implies that conducting animal experiments may be necessary to effectively test their efficacy.
  7. Lastly, he kindly offers the assistance of his science assistant as a counselor for our project, and proposes conducting experiments in his laboratory.

Conjugation of Nanoparticle and Antibody

Interviewee

Screenshot of the Wall of Wonder.

Longxing CAO


School of Life Sciences

Biology
Computational Protein Design Lab

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Looking for

We are seeking guidance for various aspects of our research project. Firstly, we need effective washing agents for iron nanoparticles without surface damage. Secondly, we are exploring antibody coupling approaches, particularly the Spytag/Spycatcher system, and appreciate protein design suggestions. We also inquire about computational methods to identify proteins with strong binding and evaluating targeting efficiency in our breast cancer antibody library. Additionally, we are seeking recommendations for nanoparticle administration routes and widely used kinetic models for drug behavior. Our focus is on nanoparticle washing, antibody coupling, computational methods, administration routes, and kinetic models in our research project.

Question we asked

  1. When isolating synthesized iron nanoparticles from E. coli, we need to remove a significant amount of biomass. Do you have any recommendations for effective washing agents that can remove biomass without significantly damaging the surface composition of the nanoparticles?
  2. We currently have two approaches for coupling antibodies to the surface of iron oxide nanoparticles. The first approach involves direct coupling with isolated iron oxide nanoparticles, where the surface coating component could be phospholipids. The second approach involves first forming a layer of polyethylene glycol (PEG) on the surface, followed by coupling with PEG. Do you have any suggestions for protein design for the coupling? We have considered the Spytag/Spycatcher system.
  3. Is it possible to use our computational methods to identify proteins that can achieve strong binding between the antibody tail and the nanoparticles?
  4. Can we use our computational methods to evaluate the targeting efficiency in our current breast cancer antibody library and target database?
  5. Do you have any recommendations for our administration route?
  6. Are there any widely used kinetic models for drug behavior in the body?

Takeaways

  1. Cao suggested directly coupling the antibody to the nanoparticle due to the instability of the long-coupled structure. However, he also highlighted that chemical cross-linking lacks directionality.
  2. Additionally, Dr. Cao emphasized that the complexities associated with glycosylation during the synthesis of antibodies in E. coli could potentially impact antibody stability.
  3. Furthermore, Dr. Cao mentioned the possibility of designing a protein cage that can self-assemble with antibodies. However, he acknowledged that our current capabilities might not be sufficient for handling such a complex process.

Interviewee

Screenshot of the Wall of Wonder.

Yue ZHANG


School of Engineering

Materials Science and Engineering
Biology
Infection and immunomodulation Laboratory

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Looking for

We are seeking specific information and recommendations for our project. Firstly, we inquire about using polyethylene glycol (PEG) as an alternative coating for nanoparticles. Secondly, we discuss coupling antibodies to iron oxide nanoparticles, particularly the Spytag/Spycatcher system, and seek protein design suggestions. Additionally, we are interested in the advantages of antimicrobial peptides and their potential application in targeting efficiency. We are also seeking relevant research on target therapy for breast cancer using nanoparticles and recommendations for modeling drug pharmacokinetics and evaluating administration methods. Our inquiries revolve around alternative coatings, coupling strategies, antimicrobial peptides, breast cancer targeted therapy, and pharmacokinetics.

Question we asked

  1. Have you tried using other materials for coating the nanoparticles, such as polyethylene glycol (PEG)?
  2. We currently have two approaches for coupling antibodies to the surface of iron oxide nanoparticles. The first approach involves direct coupling with isolated iron oxide nanoparticles, where the surface coating component could be phospholipids (similar to cell membranes). The second approach involves first forming a layer of polyethylene glycol (PEG) on the surface, followed by coupling with PEG. Do you have any suggestions for protein design for the coupling? We have considered the Spytag/Spycatcher system.
  3. In terms of targeting efficiency, do you think your researched antimicrobial peptides have a higher affinity for certain pathological cells compared to traditional antibodies? Or, what are the advantages of antimicrobial peptides, and can we apply them to our project?
  4. Do you have any relevant research on targeted therapy for breast cancer using nanoparticles? Do you have any overall recommendations for our project?
  5. Have you conducted any research on the pharmacokinetics of drugs in the body? Do you have any recommendations for modeling and evaluating our administration methods and drug effects?

Takeaways

  1. Dr. Zhang believes that our system may face difficulties in carrying drugs due to the assembly of nanoparticles in E.coli. However, she suggests that we could potentially use antibacterial polypeptides to create a pore in the membrane of the nanoparticles, through which drugs can be inserted.
  2. In regards to the conjugation of antibodies with nanoparticles, Dr. Zhang mentioned three methods: azide-alkyne cycloaddition, biotin-avidin conjugation, and EDC-NHS reaction. We have found some relevant articles on this topic and will further discuss and decide on the most suitable approach.
  3. Regarding our hypothesis that the coating of nanoparticles consists of lipids, Dr. Zhang recommends observing our samples under TEM (transmission electron microscope) to determine whether there is a membrane surrounding the nanoparticles, with an approximate size of 5nm, which is consistent with the size of a biological membrane.
  4. For the characterization of components on the surface of the nanoparticles, Dr. Zhang suggests conducting Mass Spectrum analysis to identify the proteins present.
  5. Furthermore, Dr. Zhang kindly informed us that her lab has an ultra-high-speed centrifuge available for our use.

Clinical Trials

Interviewee

Screenshot of the Wall of Wonder.

Jing YANG


Graduate student of colorectal surgery

Looking for

We are seeking information on several medical research and therapy topics. Firstly, we are interested in the potential of nanoparticle-based photo-thermal therapy for target heating. Secondly, we want to explore recent advancements in using Raman spectroscopy to distinguish tumor and healthy tissue boundaries during surgery. Additionally, we are curious about the impact of drug use restrictions and the drug development process on translating scientific research into clinical trials. Overall, we are seeking insights into nanoparticle-based therapies, surgical advancements, challenges in drug development and clinical translation, and the influence of national guidelines on breast cancer therapy.

Question we asked

  1. What is the potential of photo-thermal therapy using specific nanoparticle materials in heating the targeted area?
  2. Can you elaborate on the recent advancements in using Raman spectroscopy to differentiate between tumor and healthy tissue boundaries during surgery?
  3. How do the restrictions on drug use and the cautious drug development process impact the translation of scientific research into clinical trials?
  4. Can you provide more information about the China Breast Cancer Guidelines and how they contribute to our understanding of breast cancer therapy?

Takeaways

  1. Mr. Yang highlighted the type of nanoparticle material being used and suggested exploring photo-thermal therapy as a means to heat this material.
  2. According to him, surgery is currently the most effective therapy for tumors. Additionally, he mentioned recent advancements in using Raman spectroscopy to differentiate between tumor and healthy tissue boundaries.
  3. Mr. Yang acknowledged that clinical trials often lag behind scientific research and emphasized the strict restrictions on drug use, resulting in cautious drug development.
  4. He also provided us with the China Breast Cancer Guidelines, which deepen our understanding of breast cancer therapy.

Interviewee

Screenshot of the Wall of Wonder.

Si LU


Doctor of Oncology, Medical School of Zhejiang University

Looking for

We are seeking guidance for our project involving nanoparticles conjugated with antibodies for HER2 target therapy. Specifically, we question the significance of using these nanoparticles when trastuzumab is already available. Additionally, we inquire about the feasibility of using trastuzumab as a control and seek recommendations for effective drug encapsulation in nanoparticles. We also consider exploring alternative target options and suitable methods for nanoparticle concentration determination. Overall, we are seeking guidance on nanoparticles conjugated with antibodies, control selection, drug encapsulation, target options, and concentration determination methods.

Question we asked

  1. Is using nanoparticles conjugated with antibodies meaningful if there is already a commercialized antibody, trastuzumab, for HER2 target therapy?
  2. Can trastuzumab be used as a control in our project?
  3. What is the recommendation for our project in terms of encapsulating drugs in nanoparticles to efficiently kill cancer cells and reduce side effects?
  4. Should we consider targeting other cancer cells since HER2-positive cells have already been extensively studied?
  5. How can we determine the concentration of our biosynthetic nanoparticles? Are Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) or Inductively Coupled Plasma Mass Spectrometry (ICP-MS) suitable methods for this purpose?

Takeaways

  1. Ms. Lu believed that target therapy and immunotherapy hold great promise for future oncotherapy, as antitumor specificity is a crucial consideration in this field.
  2. She also mentioned the importance of PD-L1 (Programmed Death Ligand 1) and ICB (Immune Checkpoint Blockade) as current targets in oncology therapy.
  3. With regard to our nanoparticles that target Her2+ breast cancer cells, she emphasized the need to consider the expression of the antibodies in normal cells.
  4. Based on her experience, she asserted that the function of a drug within the body (in vivo) is the most significant factor in therapy, as sometimes the effects of drugs in vivo and in vitro can be reversed.
  5. She encouraged us to conduct experiments in mice to confirm the in vivo effect of our nanoparticles.
  6. Ms. Lu also discussed the potential benefits of combination therapy involving both first-line and second-line drugs, which could increase patients' sensitivity to the treatment.
  7. She also explained that target therapy and immunotherapy are interconnected, as target therapy can stimulate the release of antigens from diseased cells, triggering immune responses.

Interviewee

Screenshot of the Wall of Wonder.

Lixian YANG


A resident doctor in the Department of Tumor Radiotherapy, Zhejiang Provincial People's Hospital

Looking for

    We seek guidance on the significance of antibody-conjugated nanoparticles for cancer therapy, particularly in HER2 target therapy, and the feasibility of using trastuzumab as a control. We also need recommendations on efficient drug encapsulation in nanoparticles, alternative target options, and methods for determining nanoparticle concentration.

Question we asked

  1. Is using nanoparticles conjugated with nanoparticle meaningful if there is already a commercialized antibody, trastuzumab, for HER2 target therapy?
  2. Can trastuzumab be used as a control in our project?
  3. What is the recommendation for our project in terms of encapsulating drugs in nanoparticles to efficiently kill cancer cells and reduce side effects?
  4. Should we consider targeting other cancer cells since HER2-positive cells have already been extensively studied?
  5. How can we determine the concentration of our biosynthetic nanoparticles? Are Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) or Inductively Coupled Plasma Mass Spectrometry (ICP-MS) suitable methods for this purpose?

Takeaways

  1. Ms.Yang thought that if we just use our nanoparticles conjugated with antibodies, the project will not be promising and meaningful since there is already some commerialized antibodies, trastuzumab for HER2 target therapy.
  2. Another way she recommended is that we can use trastuzumab as a control.
  3. So she recommended that we capsule some drug in the nanoparticles which can not only kill the cancer cells efficiently but also reduce the side effects of the original chemotherapy.
  4. Additionally she suggested we can try to target other cancer cells since HER2 positive cells have been studied too much.
  5. She noticed that we can't determine the concentration of our biosynthetic nanoparticles and she added that concentration gradient test is crucial in clinical trial so we need to figure out its concentration for further application. Later we checked out that Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) or Inductively Coupled Plasma Mass Spectrometry (ICP-MS) may be candidates.

Interviewee

Screenshot of the Wall of Wonder.

Yiran CAI


Westlake Pharmaceuticals

Westlake Pharmaceuticals CEO assistant

Looking for

We are seeking guidance for our nanoparticle project in cancer therapy. Specifically, we want to know the significance of using antibody-conjugated nanoparticles in HER2 target therapy. Can trastuzumab be used as a control? Recommendations on efficient drug encapsulation in nanoparticles, alternative cancer cell targets, and nanoparticle concentration determination methods are also sought. Overall, we aim to optimize our project in terms of antibody conjugation, drug delivery, target selection, and nanoparticle concentration.

Question we asked

  1. What are the different stages involved in clinical trials, and at which stage is our current focus?
  2. How can we increase efficiency in the early trial stage? Specifically, how can bio-synthetic nanoparticles be utilized to enhance the drug's effectiveness?
  3. How can we ensure safety as the trials progress? What measures can be taken to enhance the safety of our bio-friendly synthetic system?
  4. When considering the drug launch, how can we assess the affordability for patients? What steps should be taken to calculate the costs involved in our experiments?
  5. How does the cost of drug production relate to the technological process? What factors should be considered regarding the sequence and volume of drug production during the middle and later stages of clinical trials?
  6. In order to understand the market trend related to the signaling pathways in cancer development, what market surveys or research should be conducted?

Takeaways

  1. Ms. Cai first refers to the basic three-period clinical trials, from cells to the human body, and makes it clear that we may still be in the first stage.
  2. Then she points out that efficiency is the first concern in the early trial, so we plan to carry drugs on the bio-synthetic nanoparticles to increase their lethal effect.
  3. Furthermore, she emphasizes that safety is more important in the later trials, and we believe that our bio-friendly synthetic system appears to be safer.
  4. Lastly, she highlights that the affordability of patients is also a concern in the drug launch. Therefore, it is better for us to calculate the costs for our experiments first.
  5. Additionally, the cost is related to the technological process. She mentions that in the middle and later periods of clinical trials, the sequence and volume of drug production often become concerns for the company.
  6. In terms of the drug market, she concludes that her company focuses on the signaling pathways in cancer development. She suggests that to understand the trend of the drug market, we may need to conduct some market surveys.

Interviewee

Screenshot of the Wall of Wonder.

Chengyong DU


The First Affiliated Hospital of Zhejiang University School of Medicine

Doctor in Breast Center

Looking for

We are seeking guidance on patient-centric considerations and drug development. Firstly, we want to ensure the suitability of our questionnaire for patients, considering its technical nature and potential difficulty in understanding therapy definitions. Secondly, we are interested in understanding the primary concerns of patients regarding drug efficacy and toxicity. Additionally, we are exploring the idea of testing our nanoparticles on different types of cancer to maximize their medical potential. Overall, our focus is on patient suitability, drug concerns, nanoparticle testing, and the development process from the laboratory to the factory.

Question we asked

  1. How can we ensure that our questionnaire is suitable for patients, taking into consideration its technical nature and potential difficulty in understanding therapy definitions?
  2. What are the primary concerns of patients when it comes to a drug, particularly in terms of its efficacy and toxicity?
  3. In order to maximize the medical potential of our nanoparticles, should we consider testing them on different types of cancer?
  4. What is the recommended approach for developing a drug from the laboratory to the factory? Should we prioritize consultation with the factory as key stakeholders, rather than reaching out to patients at this stage?

Takeaways

  1. After reviewing our questionnaire, Dr. Du suggested that it is not suitable for patients as it is too technical and many patients may not understand the definitions of each therapy.
  2. He emphasized that the primary concerns for patients regarding a drug are its efficacy and toxicity.
  3. He also recommended testing our nanoparticles on different types of cancer to maximize their medical potential.
  4. Furthermore, based on his experience, he believed that the process of developing a drug from the laboratory to the factory involves multiple parties. In our case, he thought it is premature for us to reach out to patients. Instead, he proposed that we should consult directly with the factory, as they are the key stakeholders in our project.

Reference

  • Joshi, S., & Rathore, A. S. (2020). Assessment of Structural and Functional Comparability of Biosimilar Products: Trastuzumab as a Case Study. BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy, 34(2), 209-223. View more
  • Zhou, B., Liu, J., Wang, L., Wang, M., Zhao, C., Lin, H., Liang, Y., Towner, R. A., & Chen, W. R. (2022). Iron oxide nanoparticles as a drug carrier reduce host immunosuppression for enhanced chemotherapy. Nanoscale, 14(12), 4588-4594. View more
  • Yu, Q., Xiong, X. Q., Zhao, L., Xu, T. T., Bi, H., Fu, R., & Wang, Q. H. (2018). Biodistribution and Toxicity Assessment of Superparamagnetic Iron Oxide Nanoparticles In Vitro and In Vivo. Current medical science, 38(6), 1096-1102. View more
  • Vallabani, N. V. S., & Singh, S. (2018). Recent advances and future prospects of iron oxide nanoparticles in biomedicine and diagnostics. 3 Biotech, 8(6), 279. View more
  • Akhlaghi, E., Lehto, R. H., Torabikhah, M., Sharif Nia, H., Taheri, A., Zaboli, E., & Yaghoobzadeh, A. (2020). Chemotherapy use and quality of life in cancer patients at the end of life: an integrative review. Health and quality of life outcomes, 18(1), 332. View more
  • Managing Cancer | Cancer Treatment & Side Effects | American Cancer Society. View more



Conference of China iGEMers Community



The CCIC conference held from July 8 to July 10 was hosted by Hainan University and co-organized by the State Key Laboratory of South China Sea Marine Resource Utilization, the College of Tropical Crops of Hainan University, and the College of Life Sciences of Hainan University. The Youth League Committee of Hainan University, the Academic Affairs Office of Hainan University, and the Zijin College of Hainan University co-organized it. The conference was held online and offline simultaneously, marking the first time CCiC has resumed offline events since the relaxation of pandemic policies. Thousands of viewers participated in the conference through Tencent Meeting and Bilibili live broadcast. The theme of this CCiC was “Exploring the Potential of Synthetic Biology”, aimed at encouraging everyone to think about and explore the role of synthetic biology in promoting future social development.

In addition to project roadshows, the conference also invited heavyweight guests from the academic, industrial, and social science circles of synthetic biology to give exciting reports and exchange ideas on site, sharing their achievements and experiences in their respective fields with teachers and students from all over the country. Four special lectures were set up in the field of synthetic biology, with three academic keynote speakers and one industrial keynote speaker invited. They were Professor Chen Xing from Peking University, Professor Wang Baojun from Zhejiang University, Dr. Dong Yiming from ATANTARE, and Dr. Zhang Linlin from the Institute of Oceanography, Chinese Academy of Sciences. The iGEM Foundation and the 10th CCiC Organizing Committee jointly organized a vibrant workshop to provide participants with different perspectives.

Offline sharing in CCiC.

This CCiC set up four sub-venues for project roadshows, where all teams entered according to their needs to exchange and learn with other participating teams. At the conference, iGEM teams from all over China gathered together to exchange project designs and progress, collide ideas, and guests and judges provided targeted questions and suggestions for each team. Our presentation was on July 10, and to help other contestants and other audiences understand our project theme more intuitively, we also prepared a poster detailing our project work content to complement our offline display. We gained more inspiration and ideas in the exchange. At the same time, while appreciating other teams' project displays, we also improved our own results through reflection and learning.
We also actively communicated with other project teams offline.

Offline sharing in CCiC.
Offline presentation in CCiC.
Group photo in CCiC.





Westlake Future Summit



Offline sharing in CCiC.


We have participated in the First Westlake Future Summit. From the presentation at the Summit, we can take away several key points relevant to our project on biosynthesized nanoparticles for cancer targeted therapy:

1. Bioelectronic materials: The field of bioelectronic materials offers opportunities for real-time monitoring and data analysis of body functions. This could be explored to incorporate sensing capabilities into our biosynthesized nanoparticles for monitoring therapeutic response and optimizing treatment.

Bioelectronic materials.


2. Conducting polymer hydrogels: Conducting polymer hydrogels have been widely applied in neural implants, implantable sensors, and prosthetic interfaces. This suggests that incorporating conducting polymer hydrogels into our nanoparticles could enhance their functionality and compatibility with biological systems.

3. Controlled drug delivery: The use of biomaterials, such as lipid nanoparticles, liposomes, and targeted liposomes, has shown promise in controlled drug delivery. We can leverage this knowledge to design our biosynthesized nanoparticles as effective vehicles for targeted drug delivery, compatible with both hydrophobic and hydrophilic drugs.

4. Ligand/antibody coating for specific delivery: Coating our nanoparticles with ligands or antibodies can improve their specificity and target specific cancer cells, thereby enhancing the efficacy of the therapy.

Lipid Nanoparticles.


5. PEGylation for increased drug circulation half-life: PEGylation, a process of attaching polyethylene glycol (PEG) chains to nanoparticles, can reduce immune responses and increase the circulation half-life of the drugs. This approach can be considered to improve the pharmacokinetics and therapeutic efficacy of our biosynthesized nanoparticles.

Overall, the presentation highlights the potential of bioelectronic materials, conducting polymer hydrogels, and biomaterials for controlled drug delivery. It also emphasizes the importance of specific targeting, compatibility with various drugs, and strategies to enhance drug circulation half-life. These insights can inform our approach in developing biosynthesized nanoparticles for targeted cancer therapy, making them more effective and suitable for clinical applications.

Descriptions: Additionally, we have actively engaged with stakeholders, including patient advocacy groups, healthcare providers, and pharmaceuticals companies, to gather insights and address concerns related to safety.




Healthcare Providers



After conducting interviews with numerous doctors, it has been found that patients do not have significant emphasis on the details of their therapies. As a result, it is believed that the main stakeholders for the biosynthetic nanoparticles for cancer target therapy project are pharmaceutical companies and clinicians. This conclusion is supported by the study titled "Knowledge is not power for patients: A systematic review and thematic synthesis of patient-reported barriers and facilitators to shared decision making" by Natalie Joseph-Williams et al. (2014). The results support the view that many patients currently can't participate in shared decision making (SDM) since they lack many detailed knowledge of their therapies. Therefore, it supports the notion that pharmaceutical companies and clinicians would be key stakeholders in the implementation and utilization of biosynthetic nanoparticles for cancer target therapy.

Summary of Interview with Doctors.




Patient Advocacy Group


Pink Ribbon Association Logo.


We have communicated with Pink Ribbon Association, a nonprofit organization which cares for breast cancer patients and they agreed to help us distribute our questionnaire designed for breast cancer patients. But we received few results which indicates that they know few about details of their therapies confirms that pharmaceutical companies and clinicians would be key stakeholders of our project.






Pharmaceuticals Company


Pink Ribbon Association Logo.

We have reached out to Westlake Pharmaceuticals in September and their CEO assistant has communicated with their research and development directors and gave us comprehensive feedback on our biosynthesized nanoparticles for cancer targeted therapy project. During our communication, Ms. Cai, the CEO assistant, provided us with valuable insights and guidance by highlighting clinical trial stages, efficiency, safety, affordability, and market trends. Overall, our communication with Westlake Pharmaceuticals, facilitated by Ms. Cai, has shaped and advanced our biosynthesized nanoparticles for cancer targeted therapy project.






College Vitamin



On the evening of September 26th, we had the opportunity to deliver a comprehensive lecture of College Vitamin Series to the incoming freshmen of Westlake University. During the lecture, Shijie HE systematically introduced the concept of the International Genetically Engineered Machine Competition (iGEM) and provided an in-depth overview of our team's project. The aim was to familiarize the students with the intricacies and significance of iGEM while showcasing the potential of our own project.

College Vitamin Poster.

The lecture proved to be an interactive session as the freshmen actively participated and shared their valuable feedbacks. Specifically, their insights highlighted the need for adjustments to the project's timeline, as the initial design had inadvertently resulted in an overly tight schedule for the later stages. They also pointed out the fact that our team members didn't cooperate that well. The feedbacks served as a valuable lesson, prompting us to refine our project plan and teamwork to ensure a more efficient timeline and collaboration moving forward. Furthermore, the lecture provided a platform to address the freshmen's misconceptions and misunderstandings about iGEM. Through engaging discussions and clarifications, we managed to dispel any confusion and offer a clearer understanding of the competition's objectives, rules, and the potential impact that iGEM projects can have in the field of synthetic biology.

College Vitamin.




Ethics Declarations



The questionnaire of our project was approved by Pink Ribbon Association and Dr.Du Chengyong.




Reference

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  • Bandyopadhyay, A., Das, T., Nandy, S., Sahib, S., Preetam, S., Gopalakrishnan, A. V., & Dey, A. (2023). Ligand-based active targeting strategies for cancer theranostics. Naunyn-Schmiedeberg's archives of pharmacology, 10.1007/s00210-023-02612-4. Advance online publication. View more
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