Advances in mesoporous silica nanoparticles for targeted stimuli-responsive drug delivery: an update

Abstract

Introduction: Mesoporous silica nanoparticles (MSNs) are outstanding nanoplatforms for drug delivery. Herein, the most recent advances to turn MSN-based carriers into minimal side effect drug delivery agents are covered.

Areas covered: This review summarizes the scientific advances dealing with MSNs for targeted and stimuli-responsive drug delivery since 2015. Delivery aspects to diseased tissues together with approaches to obtain smart MSNs able to respond to internal or external stimuli and their applications are here described. Special emphasis is done on the combination of two or more stimuli on the same nanoplatform and on combined drug therapy.

Expert opinion: The use of MSNs in nanomedicine is a promising research field because they are outstanding platforms for treating different pathologies. This is possible thanks to their structural, chemical, physical and biological properties. However, there are certain issues that should be overcome to improve the suitability of MSNs for clinical applications. All materials must be properly characterized prior to their in vivo evaluation; furthermore, preclinical in vivo studies need to be standardized to demonstrate the MSNs clinical translation potential.

Keywords: Mesoporous silica nanoparticles; biomedical applications; stimuli-responsive drug delivery; targeting.

Figure 1

Transmission electron microscopy of several kinds of MSNs for different biomedical applications, showing (1^st row) center-radial porosity (MSN_R) with different particle and pore size (2-12 nm); (2^nd row) longitudinal or 2D-hexagonal structure (MSN_L) with different particle size (150-50 nm); (3^rd row) MSNs coated with different inorganic nanoparticles such as gold nanorods (MSN-AuNR); gold nanoparticles (MSN-AuNPs), silver nanoparticles (MSN-AgNPs) and magnetite nanoparticles (MSN-Fe₃O₄); (4^th row) core@shell structure with hydroxyapatite nanorods (HA_NR), gold nanorods (AuNR) and magnetite nanoparticles (Fe₃O₄) as core.

Figure 2

Main factors influencing MSNs biodistribution and its accumulation in defense organs.

Figure 3

(Top) Schematic representation showing the more representative approaches described up to date, PEGylation and zwitterionization, to increase the resistance of non-specific protein adsorption and the stealthy to the macrophages. (Bottom) Confocal microscopy studies showing the macrophage-uptake of different MSN-type systems (bare MSNs, MSN-Zwitter and PEGylated MSN). The staining corresponds to cell-nuclei (DAPI, blue), cell membrane and cytoskeleton (phalloidin, red) and nanoparticles (fluorescein, green). Internalized nanoparticles are highlighted with yellow arrows, while those located in the outer area are marked with white arrows. Scale bar: 5 μm.

Figure 4

Different strategies to provide active targeting to MSNs.

Figure 5

Schematic representation of internal or endogenous stimuli to the pathological microenvironments (pH, redox, enzymes and small molecules) and external or exogenous (magnetic field, light, temperature and ultrasounds) stimuli that can be used to trigger on demand drug release from MSNs.