Making Tumor Targetting Nanoprobes

Apologies for the somewhat gruesome thumbnail image of the mice above.

In the summer of 2015, I won an international scholarship, (RISE-DAAD), to work at the Institute of Radiopharmaceutical Cancer Research in Dresden, Germany.

As part of a DAAD-RISE Scholarship, I worked under Dr. Holger Stephan at the Helmholtz-Zentrum Dresden-Rossendorf in Dresden, Germany. Together with his then PhD student Karina Pombo-Garcia (and now Dr. Karina Pombo-Garcia, congratulations Karina!) we are creating Au nanoparticle ”probes” capable of targeting tumor cells. Karina’s current project is to create magnetite nanoparticle probes with the same functionalities. The project idea was thought of by Dr. Bim Graham and Dr. Leone Spiccia of Monash University and together with Karina they synthesized the ligands prior to my arrival.

I am not going to talk about results because the work is unpublished, but I will discuss high level things.

So what is the goal? Killing cancer cells? Nope. We want to find cancer. We want to coat tumor cells in our nanoparticle substrate, and because there are a ton of imaging modalities we are going to add to the surface of the nanoparticle as well, we can image the tumor in 3+ kinds of methods.

There is a wide size distribution to most nanomaterials. By wide I mean 5 nm plus or minus a couple nanometers (95% CI). You may think, "whats a couple nanometers when its already 5 nm?". Well it turns out its a big deal! I illustrated the size distribution in the above slide. This was indeed at the peak of my Powerpoint illustration days.

I think I got a bit more lazy with the macrophage graphics here... But yes, this is the gist, macrophages will suck up nanoprobes.

Okay great, we have narrow size distribution of nanoparticles and with low surface charge, now what? How do we use them? Well there exists a type of tumor that is known to over express a type of receptor. If we can bind our nanoparticles to these tumors, we are in business. So how do we do that?

Some antibodies are the keys to some receptors locks. What if we were to stick a key on each particle?

Neat, so lets do that. We know there is 10 billion nanoparticles in a mL of solvent, can we add just the right amount of antibodies such that we get a ratio of one antibody per one nanoparticle?

And thats it! Now we have a system that can be injected into the blood, diffuse through the body and accumulate in higher statistical significance in cells that over express one type of receptor. It is able to evade the immune system and the tumor will be imaged using three types of methods.

Well, easier said than done!