As a child, many of us enjoyed playing with ‘Lego’ blocks, spending countless hours creating things. As an adult, I continue to indulge in building things, albeit on a nanoscale, much smaller than what you can see with your eyes or even standard microscopes. When we reach incredibly small sizes (one-thousandth of the width of a hair follicle), we are able to access tremendous properties and phenomena that have never been seen before. Scientists and engineers have had great success exploiting these properties across a wide domain of applications, from carbon capture to drug delivery to shrinking humans down to the size of ants. Ok, the last one might not actually be true.
At these nanoscales, a new class of materials has emerged over the past couple of decades that use building blocks made of charged metallic atoms and organic molecules to access a wide array of structures, shapes, and sizes in a manner very similar to our favorite childhood game. These materials, scientifically termed ‘metal-organic frameworks’ or ‘MOFs’, have tremendously high surface areas (the equivalent of an area of a football stadium per gram of material). And these materials can have up to ninety percent of their volume unoccupied. These features make MOFs particularly porous, and this property comes in handy for storage, separation, and delivery applications.
My project aims to employ these materials for transporting therapeutic drugs into pancreatic cancer cells. These drugs in themselves are very good at killing cancer cells. The main challenge is not the design of the drugs but rather devising mechanisms for their targeted delivery. Despite their efficacy, these drugs are not very smart because once released into the body, it does not know where to go. As a result, very high doses need to be administered for the right amount (which is often small) to reach their intended target. These high doses wreak havoc on healthy organs, causing shrinkage, and damage, resulting in a poor prognosis. Among cancers, pancreatic cancer has the poorest prognosis (median five-year survival rates are less than five percent), making their treatment an urgent need for society.
The idea is to design MOFs as vehicles for the targeted delivery of therapeutic agents into pancreatic cancer cells. As mentioned, MOFs are created from the building blocks of charged metallic atoms and organic molecules. Given that there are more than a dozen usable metallic atoms and virtually infinite organic molecules, choosing the right pair is not straightforward. I will adopt computational approaches such as high-throughput screening, first-principles calculations, and statistical methods to shortlist a candidate list of MOFs. Employment of machine learning will follow the above process to predict the properties of the MOFs. Should the need arise, a ChatGPT for molecules may also be built for formulating new organic molecules with enhanced properties in a biological context. Once an ideal set of delivery vehicles have been conceptualized, designed, and computationally validated, the next step would be their experimental synthesis and testing, initially from a laboratory scale, all the way to a clinical level.
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Written by: Dhruv Menon1,2
1. Cavendish Laboratory, Deparment of Physics, University of Cambridge, Cambridge UK.
2. Adsorption and Advanced Materials Laboratory (A2ML), Department of Chemical Engineering & Biotechnology, University of Cambridge, Cambridge UK.
NanoDTC PhD Student, c2022