Mesoporous Silica Nanoparticles for Protein Protection and Delivery

Abstract

Therapeutic proteins are widely used in clinic for numerous therapies such as cancer therapy, immune therapy, diabetes management and infectious diseases control. The low stability and large size of proteins generally compromise their therapeutic effects. Thus, it is a big challenge to deliver active forms of proteins into targeted place in a controlled manner. Nanoparticle based delivery systems offer a promising method to address the challenges. In particular, mesoporous silica nanoparticles (MSNs) are of special interest for protein delivery due to their excellent biocompatibility, high stability, rigid framework, well-defined pore structure, easily controllable morphology and tuneable surface chemistry. Therefore, enhanced stability, improved activity, responsive release, and intracellular delivery of proteins have been achieved using MSNs as delivery vehicles. Here, we systematically review the effects of various structural parameters of MSNs on protein loading, protection, and delivery performance. We also highlight the status of the most recent progress using MSNs for intracellular delivery, extracellular delivery, antibacterial proteins delivery, enzyme mobilization, and catalysis.

Keywords: drug delivery; mesoporous silica nanoparticles; mesostructure; protein therapeutics; surface modification.

Figure 1

Enhanced stability and activity of lysozyme after loaded inside the mesopores of MSNs. Schematic illustration (A) showed the relative activity of lysozyme loaded into MSNs was 4.4-folds higher than that loaded on the outer surface of solid silica nanoparticles (SSN). (B,C) showed the pore structure of MSNs and (D) showed the circular dichroism (CD) spectrum of free lysozyme and the one loaded inside MSNs. Reproduced with permission from Kao et al. (2014), The American Chemical Society.

Figure 2

MSNs with radial pore structure and their application for large protein (β-Gal) delivery. (A–C) showed the structure of MSN-CC and (D) shows the intracellular delivery of β-Gal. (E–G) showed the structure of amino group modified hollow MSNs with radial pores. (H) showed the highest β-Gal delivery efficacy ** p < 0.01. Reproduced with permission from Xu et al. (2015), The Wiley-VCH and Meka et al. (2016), The Wiley-VCH.

Figure 3

Responsive MSNs based protein delivery system for cancer therapy. Schematic drawing (A) showed the synthesis of biodegradable diselenide-bridged MSNs [TEM images in (B)] with dual-responsive and cancer cell membrane mimetic surface modification was used to deliver RNase A into cancer cells (C) and inhibit tumor growth in vivo (D). Reproduced with permission from Shao et al. (2018), The Wiley-VCH.

Figure 4

MSNs delivered proteasome to degrade tau aggregates, a pathological hallmark of Alzheimer's disease. Panel (A) was the schematic illustration and (B,C) showed the SDS-polyacrylamide gel electrophoresis (PAGE) staining of MSNs- proteasome interaction. Panel (D) showed the TEM images of MSNs and proteasome loaded MSNs. Hydrolysis assay (E) and western blots studies (F) demonstrated the degradation of tau aggregates, indicating the delivery of active form of proteasomes by MSNs. Reproduced with permission from Han et al. (2014), The Nature Publishing Group.

Figure 5

MSNs based glucose responsive insulin delivery system (A–C). Hollow MSNs (D) was used to loaded insulin and functionalized with glucose responsive layers through enzyme-polymer layer-by-layer coating strategy (E). In vivo studies showed MSNs based nanosystem enables a fast glucose response insulin release and regulates the glycemia levels in a normal range up to 84 h with a single administration (F). Reproduced with permission from Xu et al. (2017), The American Chemical Society.

Figure 6

Mesoporous silica nanoparticles for the delivery of antimicrobial protein into biofilm. MSNs for lysosome delivery. (A) the schematic drawing of MSNs delivery for biofilm. Panel (B) showed the TEM image of MSNs and (C) the penetration of MSNs into biofilm. The antibacterial performance was tested towards E. coli biofilm (D). Reproduced from Xu et al. (2018) and by permission of The Royal Society of Chemistry.