Ultrasmall tadpole-shaped nanoparticles for drug delivery

Nanoparticles are widely explored for drug delivery and have entered the market, such as in mRNA vaccines. However, many challenges remain, such as the difficulty of targeting specific sites, despite the concept of targeted delivery being widely promoted. One reason is the formation of a protein corona that covers the surface of the carefully engineered nanoparticles. In our work, we try to combat this by reducing nanoparticle size to limit protein attachment. These nanoparticles need to be larger than 5 nm to avoid renal clearance, but ideally below 10 nm. This will be achieved using sing-chain nanoparticles. The underlying polymer structure can incorporate a wide range of functionalities, such as drug molecules and targeting ligands, but the key to successful drug delivery lies in balancing these functionalities and the monomer sequence. Among different systems, we focus on polymers with pendant sugar groups, so-called glycopolymers. While single-chain nanoparticles based on glycopolymers already display good targeting of GLUT transporters, which are overexpressed on many cell lines, polymer structures that resemble tadpoles were found to be superior.