Rapid developments in the polymerization-induced self-assembly (PISA) technique have paved the way for the environmentally friendly production of nanoparticles with tunable size and shape for a diverse range of applications. In this feature article, the biomedical applications of PISA nanoparticles and the substantial progress made in controlling their size and shape are highlighted. In addition to early investigations into drug delivery, applications such as medical imaging, tissue culture, and blood cryopreservation are also described. Various parameters for controlling the morphology of PISA nanoparticles are discussed, including the degree of polymerization of the macro-CTA and core-forming polymers, the concentration of macro-CTA and core-forming monomers, the solid content of the final products, the solution pH, the thermoresponsitivity of the macro-CTA, the macro-CTA end group, and the initiator concentration. Finally, several limitations and challenges for the PISA technique that have been recently addressed, along with those that will require further efforts into the future, will be highlighted.

Polymerization-induced self-assembly (PISA) is a widely used technique for the synthesis of nanoparticles with various morphologies including spheres, worms, and vesicles. The development of a PISA formulation based on reversible addition–fragmentation chain transfer (RAFT) aqueous emulsion polymerization offers considerable advantages such as enhanced rate of polymerization, high conversion and environmentally friendly conditions. However, this formulation has typically produced spheres as opposed to worms and vesicles. Herein, we report the formation of vesicle morphology by increasing the RAFT end-group hydrophobicity of the macromolecular chain transfer agent or manipulating the radical initiator concentration used in the aqueous emulsion polymerization PISA formulation. Additionally, decreasing the molecular weight of the hydrophobic polystyrene domain in these vesicles leads to the formation of worms. This work demonstrates that RAFT end-group hydrophobicity and radical initiator concentration are key parameters which can be exploited to enable access to sphere, worm, and vesicle morphologies via the RAFT aqueous emulsion polymerization.

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The size and surface chemistry of nanoparticles dictate their interactions with biological systems. However, it remains unclear how these key physicochemical properties affect the cellular association of nanoparticles under dynamic flow conditions encountered in human vascular networks. Here, the facile synthesis of novel fluorescent nanoparticles with tunable sizes and surface chemistries and their association with primary human umbilical vein endothelial cells (HUVECs) is reported. First, a one-pot polymerization-induced self-assembly (PISA) methodology is developed to covalently incorporate a commercially available fluorescent dye into the nanoparticle core and tune nanoparticle size and surface chemistry. To characterize cellular association under flow, HUVECs are cultured onto the surface of a synthetic microvascular network embedded in a microfluidic device (SynVivo, INC). Interestingly, increasing the size of carboxylic acid-functionalized nanoparticles leads to higher cellular association under static conditions but lower cellular association under flow conditions, whereas increasing the size of tertiary amine-decorated nanoparticles results in a higher level of cellular association, under both static and flow conditions. These findings provide new insights into the interactions between polymeric nanomaterials and endothelial cells. Altogether, this work establishes innovative methods for the facile synthesis and biological characterization of polymeric nanomaterials for various potential applications.