Science AMA Series: Hi Reddit, I’m Marilyn Mackiewicz, a Research Assistant Professor of Chemistry at Portland State University. I use tiny pieces of gold to create technologies for the diagnoses and treatment diseases like macular degeneration and cancer. Ask me anything!

Abstract

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Why gold? What are the advantages of using gold over other metals? What specific attributes of gold assist with what specific processes/methods?

#curiousNotConfrontational

PerilousGourd

To follow up on the previous Reddit followers commented. It is stable, greater nanoparticle control of shape and size allowing you to tune the optical and electronic properties, and it is biocompatible. In addition, it is can be used for X-ray CT imaging and photoacoustic imaging. Mostly recently, in collaboration with our partners at the Casey Eye Institute at Oregon Health and Science University (Dr. David Huang), and the Oregon Primate Center (Dr. Trevor McGill) we are also exploring their use as optical coherence tomographic imaging (OCT) for visualizing the localization and migration of retinal stem cells intended to repair age-related macular degeneration.


In layman terms, how do the techniques for early detection and treatment, involving these new technologies, work?

PerilousGourd

For early detection, designing nanoparticles that can recognize disease states are important. For example, a multi-functional nanoparticle that would allow you to detect cancer cells early, deliver drugs at the site of tumor development with a built-in imaging agent (gold nanoparticle) would have a huge impact in cancer therapy. We are working on designing multi-functional nanoparticle platforms that would only recognize cancer cells, thereby minimizing the toxicity associated with traditional chemotherapeutics. As synthetic chemists, we decorate the surface of the gold nanoparticle with molecules that are associated with cancer cells, which helps the nanoparticles identify the cancer cells, and with drugs that shut down the pathways in cancer cells that allow the cancer to proliferate. You can think of the gold nanoparticle as a drug delivery vehicle, with a GPS molecule that takes the gold nanoparticle to its destination (the cancer cell).


In your opinion are we close to any new breakthrough treatment for macular degeneration?

jrf_1973

Over 10 million elderly people are visually impaired as a result of dry age-related macular degeneration (AMD), for which there is no effective treatment. Although there is no clinically approved treatment in the United States that would restore vision to the eye, some drugs, such as Lucentis, may be able to slow or improve vision loss. Other treatments include laser treatment or implantable telescopes. However, most treatment methods are mostly performed with patients with wet AMD.

Cell transplantation is a promising prospective therapy for retinal degenerative diseases and is currently being investigated in multiple clinical trials as a neuroprotective strategy that have been shown to repair and reverse blindness. However, one of the challenges in this area is that characterization of these cell-based therapies rely on specific information regarding cell survival, migration, and integration in the host that is primarily derived from post-mortem histological assessments. This is time consuming and difficult. We are working with Casey Eye Institute at Oregon Health and Science University (Dr. David Huang) and the Oregon Primate Center (Dr. Trevor McGill) to overcome this limitation of this technology by developing retinal STEM cell labeling using gold nanoparticles as cell-labeling contrast agents that can be used by researchers to assess the distribution, survival, migration, and differentiation of transplanted cells as well as track their location and rate of integration into the host retina in vivo using optical coherence tomography.


I'm a huge fan of nanotechnology but only in high school. I have a few questions and I hope you answer them.

(1) I would like to know what drove you to study this area and how do you guys diagnose diseases.

(2) what would be your aims for the future of medicine in nanotechnology and how will you go about it

(3) what other materials are you looking into that might help in the future ?

Thank you so much if you answer these

Samcast112

1) I was always fascinated by how drugs work when doctors prescribed them. That led me down a path to being a chemist. I am not able to diagnose diseases but I hope that technologies I develop will be able to do both diagnosis and treatment. I have also had people close to me who battled cancer and dementia, which was difficult to watch. So for personal reasons I am driven to work in this area if what I do in some small measure helps save others 2) A long term vision is for us to be able to have nanotheranostics approved and used in vivo in the clinic. By carefully thinking about nanoparticle design features and understanding nanoparticle-biological interactions we hope to overcome some of the limitations of their use in practice.
3) We are working on other types of nanoparticles that can be used for other widely used imaging techniques such MRI. Here we are particularly interested in developing gadolinium and iron oxide nanoparticles.


How are the nano particles controlled / guided to target specific areas?

peelo2311

By decorating the surface of the nanoparticle with molecules that recognize specific types of cells, one can target nanoparticles to individual cancer cells. For example, using molecules such as HER2 proteins, antibodies, folic acid, and cell penetrating peptides, etc. For information on targeted therapies. https://www.mycancergenome.org/content/molecular-medicine/overview-of-targeted-therapies-for-cancer/


What kind of nanostructures are the gold particles used in and how do these nanostructures interact with the human body to combat these diseases?

Awesome5auce

Gold nanoparticles are metal-based nanostructures and are not inherently toxic as someone already commented on. However, the method of preparation, molecules on the surface, and impurities can affect their toxicity. When designing these nanomaterials, we use naturally occurring molecules and water (commonly referred to as green synthetic approaches) to minimize any unwanted toxicity. We also coat the nanoparticle surface with molecules that are biocompatible such as peptides and lipids, which are naturally found in the body. For more about our designs: https://link.springer.com/protocol/10.1007%2F8623_2016_8 http://pubs.rsc.org/en/content/articlepdf/2008/cc/b801525b http://web.pdx.edu/~mackiewi/main.html# We use these design strategies to target cancer cells for drug delivery. A great part of what we do is modify the surface so that we can influence recognition in specific cells such as cancer cells. We are currently studying their nanoparticle-cell interactions to understand how nanoparticles are internalize and to evaluate how long they stay in a cell. We do these studies to so we can better understand how the features of nanoparticles influence their uptake and retention in cells we are targeting.

Drugs can be incorporated into the platform to kill the cancer cells by shutting down specific pathways that allow them to proliferate or the nanoparticles can serve as photothermal agents allowing us to use heat to kill them. Those are just a few ways to kill cancer cells for example.


Hi Marilyn. Macular Degeneration is something that I see in various stages on a daily basis. Would detection be possible prior to the appearance of Drusen? Currently, with drugs such as Avastin and Eylea being the recommended treatment for Neovascular AMD, what treatment(s) might this research make available to us in the near future?

Ltlmscantbwrong

Though I am not an expert in macular degeneration disease progression, let me do my best to answer this question, because it is interesting. It is possible that we could design an imaging agent to detect the early appearance of Drusen. Then, its removal would be a possible strategy. However, the best strategy right now is making some lifestyle changes that would minimize the risk and the speed of disease progression. As I understand it, simply having Drusen doesn’t predict getting advanced stages of AMD. With respect to what we are working on, we hope to use gold nanoparticles as cell-labeling contrast agents that can be used by researchers to assess the distribution, survival, migration, and differentiation of transplanted therapeutic stem cells as well as track their location and rate of integration into the host retina in vivo using optical coherence tomography. This will give us information about using stem cells as a new form for therapy for AMD in the future. Cell transplantation is a promising prospective therapy for retinal degenerative diseases. It is currently being investigated in multiple clinical trials as a neuroprotective strategy. This transplantation has been shown to repair and reverse blindness. We hope to help speed the process of its use with our technology if we can better understand the process of repair.


Hi Dr. Marylin! I am a student at PSU who really wants to start doing research. Do you have any room for an undergrad to join in? I can wash beakers and stay out of the way :)

cheorb

I am always happy to speak with students about our research and help you to determine if my lab is the right fit for you. Send me an email.


In easy to understand terms, what's been the greatest and most exciting/promising thing you have discovered? What results have left you surprised that you weren't expecting?

cookiesandpizza247

We have a new, patent-pending gold nanoparticle platform that has some very unique features that we believe can be used for many different applications. Simply put, we’ve shielded the surface of the nanoparticles we’ve designed in the lab to minimize interactions with biomolecules that might cause the nanoparticles to become destabilized. These are hybrid lipid-coated gold nanoparticles. My group thinks that these are super cool. What we do is decorate the surface of the nanoparticles with various molecules. We can make these silver and gold hybrid nanoparticles any size or shape. For reference see the links below: http://pubs.rsc.org/en/content/articlepdf/2008/cc/b801525b https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930195/pdf/nihms194344.pdf


Have you experimented with graphene?

ronigurli

I have not experimented with graphene at this point in time. We mainly focus on metal based nanoparticles and the chemistry on the surface, as this will help tune the surface architecture to enhance biocompability, nanoparticle-biological interactions, cellular uptake and recognition. There is so much to do just in the surface architecture design that would lead to nanoparticle platforms that would not be quickly eliminated from the body.


What is your vision for creating patient personalized nanoparticles? Would each patient require different ligands on their delivery system? How can you figure out what system each person needs?

aggiechemist

I envision nanoparticles personalized to each patient based on the type of cancer they have. To do this we must understand cancer biology to help guide our design for personalized medicine. Cancer genomics -- the study of the totality of DNA sequence and gene expression between tumor cells and normal host cells -- is an area that can help propel drug discovery and therapeutic interventions. Personalized vehicles can result from the use of recognition epitopes on certain cancer cell types as well as through the use of gene therapy. Here is an article that talks about this in greater detail: http://www.nature.com/nrc/journal/v15/n12/abs/nrc4015.html


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