Microfluidic-Assisted Fabrication of Dual-Coated pH-Sensitive Mesoporous Silica Nanoparticles for Protein Delivery

Abstract

Microfluidics has become a popular method for constructing nanosystems in recent years, but it can also be used to coat other materials with polymeric layers. The polymeric coating may serve as a diffusion barrier against hydrophilic compounds, a responsive layer for controlled release, or a functional layer introduced to a nanocomposite for achieving the desired surface chemistry. In this study, mesoporous silica nanoparticles (MSNs) with enlarged pores were synthesized to achieve high protein loading combined with high protein retention within the MSN system with the aid of a microfluidic coating. Thus, MSNs were first coated with a cationic polyelectrolyte, poly (diallyldimethylammonium chloride) (PDDMA), and to potentially further control the protein release, a second coating of a pH-sensitive polymer (spermine-modified acetylated dextran, SpAcDEX) was deposited by a designed microfluidic device. The protective PDDMA layer was first formed under aqueous conditions, whereby the bioactivity of the protein could be maintained. The second coating polymer, SpAcDEX, was preferred to provide pH-sensitive protein release in the intracellular environment. The optimized formulation was effectively taken up by the cells along with the loaded protein cargo. This proof-of-concept study thus demonstrated that the use of microfluidic technologies for the design of protein delivery systems has great potential in terms of creating multicomponent systems and preserving protein stability.

Intracellular Protein Delivery: Approaches, Challenges, and Clinical Applications

“…Methods to precisely tune porosity, pore size, and wall thickness of mesoporous SiNPs make these particles amenable to a variety of protein cargo including cytochrome c [ 210 ], RNase A [ 211 ], IgG [ 212 ], and ovalbumin [ 213 ]. Owing to their high surface area, mesoporous SiNPs exhibit high protein loading capacities with recent reports indicating loading capacities up to 40% protein/SiNP mass [ 214 ].…”

Droplets microfluidics platform—A tool for single cell research

“…In the past few decades, droplet microfluidics technology has developed rapidly, and it has been used in the design of microreactors because of its strong controllability in performing various operations ( Chen et al, 2022 ; Jobdeedamrong et al, 2023 ). Due to their compatibility with many chemical and biological reagents, droplet microfluidic systems have been used to prepare complex reactants and special materials, such as polymer particles ( Juang and Chiu, 2022 ), microgel particles ( Rojek et al, 2022 ), and nanoparticles ( Küçüktürkmen et al, 2022 ; Maged et al, 2022 ; Niculescu et al, 2022 ). Moreover, droplet microfluidics is widely used in biomedical research due to their simple and easy operation and high-throughput encapsulation capability.…”

Semi‐solid 3D printing of mesoporous silica nanoparticle‐incorporated xeno‐free nanomaterial hydrogels for protein delivery

“…The Therm Control Software V 2.1.5 was utilized to generate a plot of the fluorescence intensity (F350/F330) ratio against the temperature, and the melting temperature (Tm), the temperature at which half of the protein is unfolded, was determined using the inflection point (IP350/330) from the first derivative. [50] 3.8.3…”