Apologies for the radio silence from the Open Bio crew, as you can imagine we’re all holed up revising for our final ever exams! Always with her ear to the ground of the protein world, our favourite pro-geek Laura saw this new tech release from Massachusetts Institute of Technology and has done a good job at summarising it for us. At the moment this is envisaged for cancer drug delivery, where combination treatment is vital to attempt to target the multiple mechanisms involved in tumorigenesis. However the same technology would be ideal for many other diseases, and I’ll be sure keep an eye out for where this technology leads to in the future. Over to you Laura!
Chemists at MIT have devised a new way to attach three drugs commonly used to treat ovarian cancer into a single nanoparticle – in precisely controlled ratios.
On one hand, combination chemotherapy with two or more drugs helps avoid drug resistance by employing distinct mechanisms of action. On the other: nanoparticle drug delivery reduces side effects of the toxic payloads and enhances therapeutic effects by improving their pharmacokinetics. A combination of the two approaches is a very promising strategy for cancer therapy – but building nanoparticles with multiple drugs, in precise ratios, which are released in synchrony – is a great challenge.
The Johnson lab nanoparticle contains a triple hit of doxorubicin (represented in red), camptothecin (small green particles) and cisplatin (the big green particle). Each is linked via a distinct chemistry so release can be controlled. Cisplatin is released upon entry to a cell (due to exposure to the antioxidant glutathione); camptothecin is released by the action of cellular esterase enzymes; and quite impressively – doxorubicin is released upon exposure to UV light.
The lab have demonstrated the particles are more effective in killing ovarian cancer cells in vitro compared to particles containing one or two drugs, and are now starting to test the particles against tumours in animal models. It will be interesting to see the organ distribution and bioavailability of these particles.
Importantly, the authors claim their methodology for producing the particles could be scaled up rapidly and efficiently to make particles containing different ratios of multiple drugs –which means it could potentially be a very useful tool for testing different multidrug cancer treatments.
Ps. For those interested in multidisciplinary research this paper is worth a read – it includes aspects of synthetic chemistry, biophysical analytical techniques, cell based assays and confocal microscopy to observe cellular internalisation.