Smart Mesoporous Silica Nanoparticles for Protein Delivery

Abstract

Mesoporous silica nanoparticles (MSN) have attracted a lot of attention during the past decade which is attributable to their versatile and high loading capacity, easy surface functionalization, excellent biocompatibility, and great physicochemical and thermal stability. In this review, we discuss the factors affecting the loading of protein into MSN and general strategies for targeted delivery and controlled release of proteins with MSN. Additionally, we also give an outlook for the remaining challenges in the clinical translation of protein-loaded MSNs.

Keywords: controlled release; mesoporous silica nanoparticle; protein delivery; stimulus responsive MSN.

Figure 1

The pore size-selective adsorption and separation of proteins on spherical SBA-15 mesoporous silica nanoparticles (MSN) at pH7.1 (A–D). (A) Merge confocal scanning laser microscopy (CLSM) image of protein adsorbed in SBA-15 (127 Å) (red, Texas Red labeled bovine serum albumin (BSA); green, Alexa Fluor 488 labeled lysozyme (LYS)). (B) Normalized protein density along with distance. (C) BSA image. (D) LYS image. The LYS adsorption in SBA-15 MSN with different pore sizes (E–H). (E) SBA-15 MSN (28 Å). (F) SBA-15 MSN (74 Å). (G) SBA-15 MSN (127 Å). (H) LYS intensity in 74 Å and 127 Å SBA-15 [55].

Figure 2

Schematic illustration of an MSN-based protein (CD44 McAb) and chemotherapy drug targeted co-delivery system and overcome multidrug resistance in MCF-7/MDR1 breast cancer cells [83].

Figure 3

(A) Schematic illustration of a double drugs co-delivery system for controlled release of bioactive G-Ins and cAMP. cAMP is confined into the MSN pore; G-Ins is modified on the surface as a pore cap. (B) Transmission electron micrograph (TEM) of boronic acid-functionalized MSN. (C)TEM of FITC-G-Ins-capped MSN [39].

Figure 4

(A) The reaction of the disulfide bond is cut off by extracellular glutathione (GSH). (B) Schematic illustration of pore structure dependent degradability organic-inorganic hybrid mesoporous silica nanoparticles in normal and cancer cells. (I) organic-inorganic hybrid composition of degradable dendritic mesoporous organosilica nanoparticles (DDMONs), (II, V, VIII) small pore MONs, (III, VI, IX) large pore DDMONs, (IV) normal cell, (VII) cancer cell. (C) Intracellular degradation of DDMONs and MONs. DDMONs incubated with B16F10 for 4 h(c1), 24 h(c2), 48 h (c3); DDMONs incubated with HEK293t for 24 h(c2), 48 h(c3); MONs incubated with B16F10 for 4 h(c1), 24 h(c2), 48 h(c3); MONs incubated with HEK293t for 24 h(c2). In vitro release of RNase A-Aco from DDMONs-poly(ethyleneimine)-b-poly (PEI) (D) and DMONs-PEI (E) in different release solutions. (F) The uptake of DDMONs-PEI/RNase A-Aco-FITC complex in in B16F10 cells after 10 h incubation. (G) Confocal images of RNase A-Aco-FITC release from DDMONs-PEI in B16F0 cells for 24 h. Cell viability of B16F10 cancer cell (H) and Hek293t normal cell (I) after incubation with DDMONs−PEI/RNase A-Aco for 48 h (** p < 0.01) [95].

Figure 5

Schematic illustration of the construction of MMP-2 enzyme-responsive mesoporous silica Nanoparticles for the co-delivery of human serum albumin and DOX and its biological effect [99].

Figure 6

Impacts of mesoporous silica nanoparticle size on hemolytic activity. TEM of mesoporous silica nanoparticles with different size: (A) MS-25, 25 nm; (B) MS-42, 42 nm; (C) MS-93, 93 nm; (D) MS-155, 155 nm; (E) MS-225, 225 nm; (F)The dynamic light scattering size (DLS) distributions of the five mesoporous silica nanoparticles; (G) Percentage of hemolysis of red blood cells (RBCs) incubation with different size MS for 3 h in various concentration. (H) The photographs of RBCs in G. Water (+) and PBS (−) are used as positive and negative control, respectively [111].