Surface-Templated Polymer Microparticle Synthesis Based on Droplet Microarrays.

Polymer microparticle synthesis based on the surface-templated method is a simple and environmentally friendly method to produce various microparticles. Unique particles with different compositions can be fabricated by simply annealing a polymer on a liquid-repellent surface. However, there are hurdles to producing particles of homogeneous sizes with large quantities and varying the shape of particles. Here, a new approach to synthesizing multiple polymer microparticles using micropatterns with wettability contrast is presented. Polymer microparticles are formed in two steps. First, a layer of poly(sodium-4-styrenesulfonate) is deposited on the hydrophilic regions by dipping and withdrawing this micropattern from a polymer solution, and an array of microdroplets is formed. A dewetting-inducing layer on the pattern is introduced, and then target polymer patches are sequentially generated on it. By annealing over Tg, the contact line of the target polymer patch is freely receded, creating a particle form. The size and shape of the microparticle can be controlled by varying the micropatterns. In addition, it is demonstrated that microparticles made of polymer blends or polymer/nanoparticle composite are easily produced. This versatile method offers the potential of surface-templated synthesis to tailor polymer microparticles with different sizes, shapes, and functionalities in various research and applications.

High-Throughput Miniaturized Synthesis of PROTAC-Like Molecules.

The development of miniaturized high-throughput in situ screening platforms capable of handling the entire process of drug synthesis to final screening is essential for advancing drug discovery in the future. In this study, an approach based on combinatorial solid-phase synthesis, enabling the efficient synthesis of libraries of proteolysis targeting chimeras (PROTACs) in an array format is presented. This on-chip platform allows direct biological screening without the need for transfer steps.  UV-induced release of target molecules into individual droplets facilitates further on-chip experimentation. Utilizing a mitogen-activated protein kinase kinases (MEK1/2) degrader as a template, a series of 132 novel PROTAC-like molecules is synthesized using solid-phase Ugi reaction. These compounds are further characterized using various methods, including matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) imaging, while consuming only a few milligrams of starting materials in total. Furthermore, the feasibility of culturing cancer cells on the modified spots and quantifying the effect of MEK suppression is demonstrated. The miniaturized synthesis platform lays a foundation for high-throughput in situ biological screening of potent PROTACs for potential anticancer activity and offers the potential for accelerating the drug discovery process by integrating miniaturized synthesis and biological steps on the same array.