Polymers for Health 3

Nanoparticles for the treatment of pancreatic cancer

Investigators:
Prof Martina Stenzel
Dr Pu Xiao
Funding: ARC DECRA

The treatment of pancreatic cancer still remains a challenge. Not only is it a debilitation disease, but compared to other cell lines pancreatic cancer lines are more resistant to uptaking drugs and nanoparticles. Therefore, pancreatic cancer cell lines represent an interesting model system to help understanding how different surface chemistries and particle sizes can affect the interaction with cells.
Gemcitabine is the most commonly used drug for inoperable pancreatic cancer. Gemcitabine resembles a nucleoside and is built in during DNA replication. One solution offered to improve the delivery is the use of nanoparticles. Most commonly investigated are liposomes or similar self-assembled structures. Although these liposomes vary in particle size and surface chemistry, they all have a significantly increased accumulation of the drug in the pancreatic tumor in common. Although these initial results are promising, the range of data so far is limited. The particle size varies to a large extend and the drug delivery approaches are so different that overall conclusions regarding an optimized carrier cannot yet be drawn.

In our lab, we are interested in understanding the interplay between the types of nanoparticles and different effects on pancreatic cancer cells. One focal point is the investigation of different pathways to bind gemcitabine to the polymer environment. Therefore libraries of functional polymers are prepared via RAFT polymerization that are either reactive towards the drug or enable the physical interaction. As a result, nanoparticles with different functionalities, sizes and shapes can be created. The nature of these nanoparticles will directly influence the uptake of the nanoparticles by cells and how they will move in our 3D-speheroid model that was built from pancreatic tumor cells.

Prerequisite to understand the relationship between particle properties and interaction with cells require often long-term studies using fluorescent microscopy techniques. Polymer nanoparticles labeled with a fluorescent dye often lack long-term stability. Quenching of fluorescence can occur in less than an hour making it impossible to gather meaningful results over a long period of time. Nanodiamonds with their non-bleaching fluorescence can address this problem. They are increasingly used as drug delivery carriers with the drug absorbed onto them. We investigate how nanodiamonds can be modified with polymers on their surface. The resulting nanodiamonds are superior to other nanoparticles allows imaging and the delivery of therapeutics simultaneously.

Figure. Light microscope (left) and fluorescent microscope (right) images of tumour cells after being incubated with nanodiamonds coated with polymers

References

• Huynh, V. T.; Pearson, S.; Noy, J. M.; Abboud, A.; Utama, R. H.; Lu, H. X.; Stenzel, M. H., Nanodiamonds with Surface Grafted Polymer Chains as Vehicles for Cell Imaging and Cisplatin Delivery: Enhancement of Cell Toxicity by POEGMEMA Coating. Acs Macro Letters 2013, 2 (3), 246-250.