Repository logo
 

Formation of Protein Nanoparticles in Microdroplet Flow Reactors.

Published version

Published version
Peer-reviewed

Repository DOI


Change log

Authors

Zhang, Qi 
Toprakcioglu, Zenon  ORCID logo  https://orcid.org/0000-0003-1964-8432
Jayaram, Akhila K 
Guo, Guangsheng 

Abstract

Nanoparticles are increasingly being used for biological applications, such as drug delivery and gene transfection. Different biological and bioinspired building blocks have been used for generating such particles, including lipids and synthetic polymers. Proteins are an attractive class of material for such applications due to their excellent biocompatibility, low immunogenicity, and self-assembly characteristics. Stable, controllable, and homogeneous formation of protein nanoparticles, which is key to successfully delivering cargo intracellularly, has been challenging to achieve using conventional methods. In order to address this issue, we employed droplet microfluidics and utilized the characteristic of rapid and continuous mixing within microdroplets in order to produce highly monodisperse protein nanoparticles. We exploit the naturally occurring vortex flows within microdroplets to prevent nanoparticle aggregation following nucleation, resulting in systematic control over the particle size and monodispersity. Through combination of simulation and experiment, we find that the internal vortex velocity within microdroplets determines the uniformity of the protein nanoparticles, and by varying parameters such as protein concentration and flow rates, we are able to finely tune nanoparticle dimensional properties. Finally, we show that our nanoparticles are highly biocompatible with HEK-293 cells, and through confocal microscopy, we determine that the nanoparticles fully enter into the cell with almost all cells containing them. Due to the high throughput of the method of production and the level of control afforded, we believe that the approach described in this study for generating monodisperse protein-based nanoparticles has the potential for intracellular drug delivery or for gene transfection in the future.

Description

Keywords

Bovine serum albumin, beta-lactoglobulin, droplet microfluidics, high-throughput nanoparticle formation, intracellular delivery, protein nanoparticles, regenerated silk fibroin, Humans, HEK293 Cells, Nanoparticles, Microfluidics, Drug Delivery Systems, Polymers

Journal Title

ACS Nano

Conference Name

Journal ISSN

1936-0851
1936-086X

Volume Title

17

Publisher

American Chemical Society (ACS)
Sponsorship
Engineering and Physical Sciences Research Council (EP/L015978/1)
European Commission Horizon 2020 (H2020) ERC (101001615)