Keynote
Designing soft polymeric nanoconstructs for vascular drug delivery and brain depots

The size, surface property and shape of nanoparticles have been quite extensively investigated in the context of drug delivery and biomedical imaging. More recently, softness is emerging as an additional design parameter for modulating the interaction of nanoparticles with cells and their biological microenvironment. By combining lithographic techniques and polymer chemistry, Discoidal Polymeric Nanoconstructs (DPNs) can be fabricated exhibiting different sizes, shapes, surface properties and mechanical stiffnesses. These are the 4S parameters – size, shape, surface, stiffness – which can be precisely tuned in the synthesis process enabling disease- and patient-specific designs of multifunctional polymeric nanoconstructs. These may have sizes ranging from the sub-micron scale (600 nm) to tens of microns (O(10) mm); different shapes, including circular, square, elliptical, rectangular and so on; surface charges varying from very negative (-50 mV) to moderately positive (+ 20 mV); and a structure as soft as cells (O(10 kPa) to as rigid as trabecular bone (O(10 MPa)). Three different applications are discussed: 1,000 × 400 nm discoidal nanoconstructs carrying thrombolytic agents for rapid vessel recanalization; 20 × 20 × 10 µm micro-plates for the long-term release of anti-inflammatory molecules in osteoarthritis; and 10 × 10 × 5 µm micro-meshes for the sustained release of chemotherapeutic nanoparticles and molecules in the treatment of brain tumors. The main focus is on fine tuning the 4S parameters and assessing their contribution to therapeutic outcome.