Targeting Cells with DNA Nanostructures
Scientists use DNA origami to improve targeted drug delivery for diseases.
Indra Van Zundert, Elena Spezzani, Roger R. Brillas, Lars Paffen, Angelina Yurchenko, Tom F. A. de Greef, Lorenzo Albertazzi, Alessandro Bertucci, Tania Patiño
― 7 min read
Table of Contents
- The Role of Nanotechnology
- The Challenge with Targeting
- DNA Origami: A Game Changer
- Real-World Applications of DNA Origami
- Challenges in Current Research
- The Next Steps
- Experimenting with DNA Nanorods
- The Experimental Setup
- Monitoring Interactions
- Observing Movement
- Binding Statistics
- Specificity Matters
- Testing Different Cell Types
- The Kinetics of Binding
- Decoding Binding Dynamics
- Implications for Future Research
- In Summary: The Bigger Picture
- Why This Matters
- Original Source
Cell surface interactions are vital for many biological processes. They help in things like how cells communicate, how our immune system works, and how cells stick together. These interactions also play a big role in keeping our tissues healthy. When something goes wrong, it can lead to diseases. So, figuring out how these interactions work can help scientists develop new medicines and tools to diagnose conditions.
The Role of Nanotechnology
Recently, scientists have seen great potential in using tiny particles, known as Nanoparticles, to target specific cell Receptors. These nanoparticles can be customized in size and have special surfaces that allow them to attach various molecules. This customization can make them more effective at targeting certain cells. For example, attaching more signals or “ligands” to a single nanoparticle can enhance its ability to find and attach to specific cell receptors.
The Challenge with Targeting
While there have been advances in using nanoparticles for targeting, controlling how many signals are on a particle and where they are positioned is quite tricky. This is where DNA Origami comes in. Using a long stretch of DNA, scientists can create shapes and structures that are precise and programmable. They can place different molecules on these DNA structures exactly where they want them, which can improve how well they target cells.
DNA Origami: A Game Changer
DNA origami allows researchers to build tiny 1D, 2D, and even 3D structures from DNA. These structures can act like little buses, carrying important molecules to specific cells. The ability to put these molecules in specific spots is crucial for targeting. Different spacing between the signals can influence how well they bind to the cells. Because of this design flexibility, DNA origami shows promise for studying how cells interact.
Real-World Applications of DNA Origami
In the last ten years, scientists have worked hard to ensure that DNA origami is safe to use in living organisms. This means making sure it won’t cause any harm or get broken down too quickly in the body. They aim to apply DNA origami to various fields, including cancer treatment, gene therapy, and vaccine development. For example, DNA origami can deliver cancer drugs directly to tumor cells, minimizing harm to healthy cells.
Challenges in Current Research
So far, most studies have looked at how well DNA origami targets cells, but there are many details still unknown. Not much is known about how DNA origami interacts with the cells on a small scale. Most research has been focused on measuring results after a certain amount of time, without looking at the initial interactions between the DNA structures and cell membranes.
The Next Steps
To fill these gaps, researchers are studying how DNA origami interacts with cell membranes right from the start. They are using a method called single particle tracking (SPT). This technique allows them to watch the movement of individual DNA structures over time. By observing how these structures diffuse, bind, and enter cells, they can gain insights into how targeted drug delivery works in real-time.
Experimenting with DNA Nanorods
In their experiments, the scientists created DNA nanorods that were functionalized with special antibodies or Aptamers. These are like little flags that help the rod find and bind to specific receptors on the surface of breast cancer cells, which have lots of a receptor called EGFR. By watching how these nanorods move and bind, the researchers can learn more about how effective their targeting methods are.
The Experimental Setup
The researchers used two types of cells: breast cancer cells (with high EGFR) and kidney cells (with low EGFR) for comparison. The goal was to see how well the nanorods could differentiate between the two kinds of cells based on the number of receptors they have. This can help establish whether their targeting approach is selective.
Monitoring Interactions
To monitor how well the DNA nanorods were Binding to the cells, the researchers captured images of these interactions. They used fancy microscopes to visualize how the DNA nanorods behaved after being introduced to the cells. By analyzing the pictures, they could tell how many rods were binding to the cells and how long they stayed attached.
Observing Movement
In their observations, non-functionalized DNA nanorods (the plain ones with no special flags) moved randomly, akin to a child running in a playground. In contrast, the functionalized nanorods showed different movement patterns when they found their target. Some would slow down near the cell surface, indicating they were successfully binding to the cell.
Binding Statistics
The researchers calculated how many of these nanorods successfully bound to the target cells over time. They noticed that the functionalized rods had a significantly higher binding percentage compared to the non-functionalized ones. This suggests that their targeting approach worked well.
Specificity Matters
Interestingly, the nanorods decorated with aptamers (one type of flag) showed a different binding pattern compared to those with antibodies (another type of flag). While the antibodies had a sharp drop in binding after an initial spike, the aptamer-coated rods increased their binding over time. This observation may indicate that aptamers can provide a stronger and more stable interaction with the target receptor.
Testing Different Cell Types
Next, researchers wanted to see how the nanorods performed on cells with lower receptor expression. By comparing the binding of nanorods to both high and low EGFR cells, they could assess how effective their targeting method was. They observed that nanorods targeted the cells more effectively with high EGFR levels, suggesting their selectivity was good.
The Kinetics of Binding
To better understand how the nanorods interacted with the receptors, the researchers examined the kinetics of these interactions. They focused on how quickly the nanorods attached to the receptors and how soon they detached. By analyzing how long the rods stayed attached, the researchers could figure out the strength of their binding.
Decoding Binding Dynamics
The outcomes revealed some surprising results. For example, even with more binding flags on the nanorods, the binding time didn’t increase significantly for antibody-decorated rods. This could be due to the larger size of antibodies causing some interference, while aptamers, being smaller, allowed for better interactions.
Implications for Future Research
The findings from these experiments shed light on how DNA origami can effectively target specific cell types. These insights have significant implications for designing better drug delivery systems. Scientists can use this knowledge to create more effective and selective treatments for diseases, including cancer.
In Summary: The Bigger Picture
In conclusion, researchers are making exciting strides in understanding how DNA origami interacts with cell surfaces. By using advanced techniques like single particle tracking, they can probe these interactions more deeply than ever before. Their findings not only enhance scientific knowledge but also open new doors for creating targeted therapies and drug delivery systems. The future looks bright as researchers continue to unwrap the mysteries of DNA nanostructures and their potential in medicine.
Why This Matters
To put it in simpler terms, the ability to target specific cells is like sending a guided missile into a target area while avoiding innocent bystanders. As scientists become more skilled at using DNA origami for such purposes, they not only improve therapies but also ensure fewer side effects for patients. In the world of science, every discovery can lead to new and better approaches to tackling complex health challenges.
And who knows? In the future, we might have nanobots zipping around in our bloodstream, delivering medicine right where it’s needed, while avoiding all the pesky traffic of our body!
Original Source
Title: Unveiling DNA Origami Interaction Dynamics on Living Cell Surfaces by Single Particle Tracking
Abstract: Due to the unique spatial addressability of DNA origami, targeting ligands (e.g. aptamers or antibodies) can be specifically positioned onto the surface of the nanostructure, constituting an essential tool for studying ligand-receptor interactions at the cell surface. While the design and ligand incorporation into DNA origami nanostructures are well-established, the study of cell surface interaction dynamics is still in the explorative phase, where in depth fundamental understanding on the molecular interactions remains underexplored. This study uniquely captures real-time encounters between DNA origami and cells in-situ using single particle tracking (SPT). Here, we functionalized DNA nanorods (NRs) with antibodies or aptamers specific to the epidermal growth factor receptor (EGFR) and used them to target EGFR-overexpressing cancer cells. SPT data revealed that ligand coated NRs selectively bound to the receptors expressed in target cancer cells, while non-functionalized NRs only display negligible cell interactions. Furthermore, we explored the effect of ligand density on the DNA origami, which revealed that aptamer-decorated NRs exhibit non-linear binding characteristics, whereas this effect in antibody-decorated NRs was less pronounced. This study provides new mechanistic insights into the fundamental understanding of DNA origami behaviour at the cell interface, with unprecedented spatiotemporal resolution, aiding the rational design of ligand-targeted DNA origami for biomedical applications.
Authors: Indra Van Zundert, Elena Spezzani, Roger R. Brillas, Lars Paffen, Angelina Yurchenko, Tom F. A. de Greef, Lorenzo Albertazzi, Alessandro Bertucci, Tania Patiño
Last Update: 2024-12-23 00:00:00
Language: English
Source URL: https://www.biorxiv.org/content/10.1101/2024.12.23.628980
Source PDF: https://www.biorxiv.org/content/10.1101/2024.12.23.628980.full.pdf
Licence: https://creativecommons.org/licenses/by-nc/4.0/
Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.
Thank you to biorxiv for use of its open access interoperability.