Versatile, Solvent-Free Technique to Synthesize Polymer Nanoparticles

Polymer nanoparticles (PNPs) represent a robust category of promising nanotheranostics as functionalizable platforms amenable to the incorporation of therapeutics and diagnostic aids into stimuli-responsive structures. Conventional bottom-up synthesis of monomers to form PNPs is performed in a liquid environment which introduces solubility- and rheology-based restrictions on the resulting morphologies and nanoparticle and therapeutic chemistries. The present work reports a new technique named condensed droplet polymerization (CDP) in which PNPs were synthesized from vapor-phase reagents without any liquid-based steps, avoiding limitations based on solubility. CDP utilizes a retrofitted chemical vapor deposition reactor to rapidly synthesize PNPs in a liquid-free environment via coupled nanoscale condensation-polymerization steps that are complete within minutes. First, condensation is controlled at the nanoscale using in situ high-resolution digital microscopy. Then, vapor phase radical initiators bombard the nanoscale droplets, initiating a polymerization that is complete in less than 30 seconds. The all-dry technique was used to synthesize non-spherical, dome-shaped PNPs featuring a range of chemistries (hydrophilic, hydrophobic, crosslinked, biocompatible) each with targeted diameters spanning from below 20 nm to above 1 μm with no changes to the standard protocol. Furthermore, the utilization of only vapor phase reagents enables novel routes to incorporating therapeutic and diagnostic molecules outside of a solution or emulsion. Through CDP, porous PNPs can also be synthesized to alter the release kinetics of a therapeutic agent from a stimuli-responsive porous particle. As a platform for the rapid synthesis of non-spherical PNPs that avoids the challenges of liquid-based techniques, CDP is a promising route to generating PNPs from materials inaccessible by other methods and provides new opportunities for incorporating theranostic agents into stimuli-responsive polymers.