Smart Mesoporous Nanomaterials for Antitumor Therapy

Abstract

The use of nanomaterials for the treatment of solid tumours is receiving increasing attention by the scientific community. Among them, mesoporous silica nanoparticles (MSNs) exhibit unique features that make them suitable nanocarriers to host, transport and protect drug molecules until the target is reached. It is possible to incorporate different targeting ligands to the outermost surface of MSNs to selectively drive the drugs to the tumour tissues. To prevent the premature release of the cargo entrapped in the mesopores, it is feasible to cap the pore entrances using stimuli-responsive nanogates. Therefore, upon exposure to internal (pH, enzymes, glutathione, etc.) or external (temperature, light, magnetic field, etc.) stimuli, the pore opening takes place and the release of the entrapped cargo occurs. These smart MSNs are capable of selectively reaching and accumulating at the target tissue and releasing the entrapped drug in a specific and controlled fashion, constituting a promising alternative to conventional chemotherapy, which is typically associated with undesired side effects. In this review, we overview the recent advances reported by the scientific community in developing MSNs for antitumor therapy. We highlight the possibility to design multifunctional nanosystems using different therapeutic approaches aimed at increasing the efficacy of the antitumor treatment.

Keywords: active targeting; cancer treatment; mesoporous silica nanoparticles; passive targeting; stimuli-responsive drug delivery.

Figure 1

Schematic depiction of drug administration for cancer therapy: systemic treatments versus targeted therapies using nanomaterials.

Figure 2

Left: Main characteristics of MSNs. Right: transmission electron microscopy (TEM) images of 2D-hexagonal MCM-41 type mesoporous silica nanoparticles (MSNs) taken with the electron beam parallel (up) and perpendicular (down) to the mesoporous channels.

Figure 3

Schematic illustration of enhanced permeation and retention (EPR) effect.

Figure 4

Molecular targets for active targeting of cancer by mesoporous silica nanoparticles: (i) tumor cell membrane receptors, such as transferrin receptors (TfR), folic acid receptors (FR-α) and lectin receptors; (ii) tumor vasculature receptors, such metalloproteinases, as αβ-integrins and vascular endothelial growth factor receptor (VEGFR). Molecular targets for active targeting of cancer by mesoporous silica nanoparticles.

Figure 5

Schematic representation of the performance of stimuli-responsive MSNs.

Figure 6

Up: Schematic illustration of the action mechanism of light-responsive nanosystem based in MSNs decorated with a biocompatible protein shell (transferrin, Tf, grafted to MSNs using a light cleavable photolinker), affording MSN-Tf. Down: Cellular uptake of MSNs and MSN-Tf labeled with fluorescein. Confocal microscopy images show NPs (green) inside tumor cells (actin in red, nucleus in blue). The light irradiation of MSN-Tf provokes the cleaving of the photolinker, which triggers pore uncapping and subsequent drug release [76].

Figure 7

Schematic illustration of the in situ cytotoxic generation for antitumor therapy [139]. (i) Functionalization of MSNs with amino group (MSN-NH₂); (ii) loading of the pro-drug indol-3-acetic acid (IAA) (MSN-NH₂-IAA); grafting of an enzyme horseradish peroxidase (HRP)-polymer nanocapsule to the external surface of the nanosystem (MSN-NH₂-IAA-HRPc). TEM images of the nanosystem and cytotoxicity studies with neuroblastoma cells are also displayed.