noc19 bt23 lec62 Targeted Drug Delivery System Research Paper Discussion

Summary

In this lecture, Prof. Rachit Agarwal discusses targeted drug delivery systems, focusing on the use of DNA nanotechnology. He explains the principles of passive and active targeting, highlighting the potential of DNA origami to create sophisticated nanostructures for cancer therapy. The lecture delves into a specific research paper on DNA nanorobots designed to block blood vessels feeding tumors, utilizing thrombin for clotting and nucleolin for targeting. Experimental results demonstrate the effectiveness of these nanorobots in reducing tumor volume and enhancing survival rates in mouse models, showcasing the promising future of targeted therapies in cancer treatment.

Takeaways

• 😀 Targeted drug delivery systems focus on delivering medication to specific cells or tissues in the body to improve therapeutic efficacy.
• 😀 Passive targeting relies on the physical properties of drug carriers, such as size and charge, to accumulate in certain areas, like tumors.
• 😀 Active targeting involves conjugating drugs with specific ligands or antibodies to enhance binding to targeted receptors on cells.
• 😀 Aptamers, small nucleotide-based molecules, can be used in targeted drug delivery due to their ability to bind specific proteins.
• 😀 DNA origami is a technique used to create complex nanoscale structures from DNA, which can be utilized for drug delivery.
• 😀 The study discusses a DNA nanorobot that uses DNA origami to selectively block blood vessels feeding tumor regions.
• 😀 Thrombin is employed to enhance platelet aggregation and promote blood clotting in tumor-targeted therapies.
• 😀 The researchers successfully modified thrombin with single-stranded DNA to create an efficient drug delivery system.
• 😀 In mouse models, the DNA nanorobots showed effective targeting of tumor blood vessels, leading to reduced tumor volume and improved survival rates.
• 😀 The results indicate that the DNA nanorobot system can outperform traditional therapies, even in poorly vascularized tumors.

Q & A

What are targeted drug delivery systems?

Targeted drug delivery systems are designed to deliver medication specifically to a certain disease, cell, or location in the body. They can utilize passive targeting based on properties like size and charge, or active targeting using specific ligands or receptors.

How does size affect the retention of particles in the body?

Particles larger than 6-10 nanometers are retained in the body longer because the kidneys cannot clear them efficiently. The Enhanced Permeability and Retention (EPR) effect allows particles sized between 50 to 200 nanometers to accumulate in tumor tissues.

What is the difference between passive and active targeting?

Passive targeting relies on physical properties such as size and charge, while active targeting involves conjugating drugs with specific ligands, proteins, or antibodies that bind to specific receptors on target cells.

What are aptamers and their role in drug delivery?

Aptamers are small nucleotide-based molecules that can bind to specific proteins through their tertiary structure. They serve as targeting agents in drug delivery systems, similar to antibodies but can be more easily synthesized and modified.

What is DNA origami in the context of drug delivery?

DNA origami is a technique that uses single-stranded DNA to fold into complex shapes at the nanoscale. It allows for the design of precise, controllable DNA nanostructures for targeted drug delivery.

How does the paper propose to block blood vessels feeding tumors?

The paper describes using DNA origami to create structures that can selectively bind to thrombin, a protein that promotes blood clotting. These structures aim to block blood vessels supplying tumors, potentially starving them of nutrients.

What is the significance of thrombin in this study?

Thrombin is significant because it upregulates platelet aggregation and helps form blood clots. In this study, it is used as a target to be bound by DNA origami structures to obstruct blood flow to tumors.

What role do nucleolin proteins play in this research?

Nucleolin proteins are selectively expressed in proliferating endothelial cells, often found in tumor-associated blood vessels. The research leverages nucleolin as a target for the DNA nanostructures, allowing them to differentiate between healthy and tumor-associated cells.

What were the key findings regarding the efficacy of the DNA nanorobots in animal models?

The study found that the DNA nanorobots effectively reduced tumor volume and weight in mouse models, leading to enhanced survival rates compared to control groups. They showed promising results in both well-vascularized and poorly vascularized tumor models.

How does this research contribute to the field of targeted nanomedicine?

This research advances targeted nanomedicine by demonstrating the use of DNA origami for precise drug delivery, enhancing the targeting specificity of therapeutic agents, and potentially improving the effectiveness of cancer treatments.