Some of the biggest challenges of nanotechnology applications to medicine and tumor treatments have been the effective delivery and clearance of nanoparticles. Cells and tumour sites can’t hold particles that are too big, and they quickly expel particles that are too small. Also, macrophages, the body’s defence against foreign bodies, often phagocytose and sequester particles depending on their size and surface chemistry, which leads to decreased particle delivery and potential immune toxicity. Furthermore, while larger particles have been shown to have more effective tumor destruction, they pose concerns, as larger particles cannot be cleared from the body and many of them are non-biodegradable, which could result in long-term toxicities.
A team of researchers at the University of Toronto has engineered modular nanoparticles that address some of these issues. The new technology employs the properties of DNA, using complementary strands to bind sub-6nm nanoparticles together and create “nanoparticle superstructures” whose sizes and functionalities can be optimized for uptake into cells by linking different numbers and types of particles together. The superstructures are then coated in a protective polymer coating called poly(ethylene glycol) (PEG). After delivery into cells, the linking DNA strands are slowly degraded over time via natural enzymatic reactions, cleaving the superstructures into their smaller building blocks. This enables their clearance from the cells and subsequent whole-body elimination.
In the study published in Nature Nanotechnology, the researchers showed that the superstructures accumulated in tumors were non-toxic to other organs, and could be eliminated through the kidneys, unlike larger solid nanoparticles.
While this breakthrough is promising and exciting for those in the field, Dr. Warren Chan, the corresponding author of the study, told U of T News and Medgadget: ”We need to understand how DNA design influences the stability of things, and how a lack of stability might be helpful or not. The use of assembly to build complex and smart nanotechnology for cancer applications is still in the very primitive stage of development. Once the basic studies are done to obtain a better understanding of the superstructure system, we can load them up with drugs or/and imaging agents and to start to move them through clinical trials and eventual use in patents.”
Provided by: by BEN OUYANG