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Review
. 2019 Apr;16(4):415-439.
doi: 10.1080/17425247.2019.1598375. Epub 2019 Apr 22.

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

Rafael R Castillo  1   2   3 , Daniel Lozano  1   2   3 , Blanca González  1   2   3 , Miguel Manzano  1   2   3 , Isabel Izquierdo-Barba  1   2   3 , María Vallet-Regí  1   2   3
Affiliations
Review

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

Rafael R Castillo et al. Expert Opin Drug Deliv. 2019 Apr.

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.

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Conflict of interest statement

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Figures

Figure 1
Figure 1
Transmission electron microscopy of several kinds of MSNs for different biomedical applications, showing (1st row) center-radial porosity (MSNR) with different particle and pore size (2-12 nm); (2nd row) longitudinal or 2D-hexagonal structure (MSNL) with different particle size (150-50 nm); (3rd 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); (4th row) core@shell structure with hydroxyapatite nanorods (HANR), gold nanorods (AuNR) and magnetite nanoparticles (Fe3O4) as core.
Figure 2
Figure 2
Main factors influencing MSNs biodistribution and its accumulation in defense organs.
Figure 3
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
Figure 4
Different strategies to provide active targeting to MSNs.
Figure 5
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.
See this image and copyright information in PMC

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