A High‐Throughput Platform for Formulating and Screening Multifunctional Nanoparticles Capable of Simultaneous Delivery of Genes and Transcription Factors

Abstract

Simultaneous delivery of multiple genes and proteins (e.g., transcription factors, TFs) is an emerging issue surrounding therapeutic research due to their ability to regulate cellular circuitry. Current gene and protein delivery strategies, however, are based on slow batch synthesis, which is ineffective, poorly controlled, and incapable of simultaneous delivery of both genes and proteins with synergistic functions. Consequently, advances in this field have been limited to in vitro studies. Here, by integrating microfluidic technologies with a supramolecular synthetic strategy, we present a high-throughput approach for formulating and screening multifunctional supramolecular nanoparticles (MFSNPs) self-assembled from a collection of functional modules to achieve simultaneous delivery of one gene and TF with unprecedented efficiency both in vitro and in vivo. We envision that this new approach could open a new avenue for immunotherapy, stem cell reprogramming, and other therapeutic applications.

Recent advances of controlled drug delivery using microfluidic platforms

“…However, conventional batch processes by bulk mixing and nanoprecipitation are technically challenging in fabricating monodisperse nanoparticles with a desired size and morphology, which compromises the properties of the produced nanoparticles [146]. Microfluidic systems have opened a new horizon for the development of novel nanoparticles as drug carriers [147, 148]. The rapid and tunable mixing in microfluidics makes it capable for precious control over the synthesis processes of nanoparticles by systematically varying parameters such as flow rates, reagent concentrations and compositions, temperature, and mixture time.…”

Microfluidic High-Throughput Platforms for Discovery of Novel Materials

“…However, it remains challenging to accurately encode the synthetic parameters of each microdroplet, thus limiting the further increasement of its throughput. Recently, a novel high-throughput method called “droplet library”, which combines a microfluidic droplet generator with microarrays, are proposed [ 75 , 113 ]. The basic principles are shown in Figure 5 .…”

Microfluidic hydrodynamic focusing for synthesis of nanomaterials

“…For emerging new applications, such as synthesis of personalized medicine, which only requires small amount of products, the slow production rate of current microfluidic HF reactors can be sufficient. However, considering the ever-growing potential of NPs in industrial applications, and to realize the translation of microfluidic devices for more general biomedical and pharmaceutical applications, it is important to scale-up the synthesis process while maintaining the advantages of microfluidics in order to achieve mass production [66,67]. …”