Playing with molecular Lego to build the next generation of drug delivery vectors

albertazzi ACS nanoMany drugs are hindered in their therapeutic potential by issues such as too-fast clearance by the kidneys, undesirable properties, lack of selectivity, and poor internalization in the cell. Nanotechnology has the potential to alter the landscape of medicine by providing targeted solutions for the delivery of small-molecule drugs and biopharmaceuticals.

Now, new IBEC junior group leader Lorenzo Albertazzi and his former colleagues at the Eindhoven University of Technology, working together with industry partner Novartis, have made a leap in drug delivery vectors by developing a new type of carrier with some groundbreaking improvements.

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“We focused on supramolecular polymers, an emerging family of nanosized structures with many potential uses in materials chemistry and medicine, to prepare them,” says Lorenzo. “Usually, the nanoparticles that are being developed for drug delivery are spherical, but our particles are fiber-shaped.”

One such polymer, BTA, is a versatile building block able to self-assemble in water into one-dimensional aggregates. Exploiting the unique modular approach of supramolecular chemistry, the researchers could co-assemble neutral and positively charged BTAs and control the overall properties of the polymer by simple mixing of monomers – molecules that bind chemically (or supramolecularly) to others.

“This unique modularity means that we essentially have a library of building blocks – a bit like a big bucket of Lego bricks in different colours – and we can combine them simply mixing the ones we like in a vial,” explains Lorenzo. “This is possible because the bricks self-assemble, means they spontaneously get together to form the fiber. For instance, if we throw in 50% “red” bricks and 50% “green” bricks, we will find them in the fiber without any effort, as the material build itself. The different bricks can have different chemical properties (e.g. charge) or different functionalities (e.g. drugs or targeting agents). In this way, we can try a lots of combinations of bricks, and check which one is the best for delivery.”

The special properties of supramolecular polymers also mean that they can carry more than one type of drug. “BTA polymers contain two compartments that can be used for intracellular delivery,” Lorenzo adds. “Small hydrophobic compounds can be encapsulated in the lipophilic core, while siRNA can be condensed on the outside via electrostatic interactions.”

The scientists demonstrated that both the siRNA and the hydrophobic molecule were successfully delivered to living cells. With the suitability of the supramolecular BTA platform for intracellular delivery confirmed, the study represents an important step in the quest to develop non-toxic, tailored, effective drug carriers, and paves the way for further research.

Maarten H. Bakker, Cameron C. Lee, E.W. Meijer, Patricia Y.W. Dankers and Lorenzo Albertazzi (2016). “Multicomponent Supramolecular Polymers as a Modular Platform for Intracellular Delivery”. ACS Nano, 10 (2), pp 1845–1852