Surface Modification of Mesoporous Silica Nanoparticles for Application in Targeted Delivery Systems of Antitumour Drugs

Abstract

The problem of tumour therapy has attracted the attention of many researchers for many decades. One of the promising strategies for the development of new dosage forms to improve oncology treatment efficacy and minimise side effects is the development of nanoparticle-based targeted transport systems for anticancer drugs. Among inorganic nanoparticles, mesoporous silica deserves special attention due to its outstanding surface properties and drug-loading capability. This review analyses the various factors affecting the cytotoxicity, cellular uptake, and biocompatibility of mesoporous silica nanoparticles (MSNs), constituting a key aspect in the development of safe and effective drug delivery systems. Special attention is paid to technological approaches to chemically modifying MSNs to alter their surface properties. The stimuli that regulate drug release from nanoparticles are also discussed, contributing to the effective control of the delivery process in the body. The findings emphasise the importance of modifying MSNs with different surface functional groups, bio-recognisable molecules, and polymers for their potential use in anticancer drug delivery systems.

Keywords: anticancer drugs; drug delivery; inorganic nanoparticles; mesoporous silica; polymers; surface modification.

Figure 5

Graphical representation of different types of nanoparticles used in biomedical applications. (Reprinted with permission from reference [66]. Copyright © 2016, The Royal Society of Chemistry).

Figure 6

Analysis of the dynamics of publications on the use of inorganic nanoparticles for targeted drug delivery. Search was performed using the combination of the keywords “inorganic nanoparticles” and “drug delivery”.

Figure 1

Stages of malignant tumour development. The positions Tis, T1, T2, T3, T4 shown in the figure correspond to the stages of tumor development stage 0, stage I, stage II, stage III, stage IV, respectively, which is also reflected in Table 1. (Reprinted with permission from the reference with changes [8]. Copyright © 1987, International Union Against Cancer Geneva.)

Figure 2

Schematic representation of drug applications for cancer treatment: conventional chemotherapy and nanomaterial-based targeting therapy. (Reprinted with permission from reference [38]. Copyright © 2015 Licensee MDPI, Basel, Switzerland.)

Figure 3

Enhanced permeability and retention (EPR) effect and passive targeting. (Reprinted with permission from reference [40] Copyright © 2014 Jhaveri and Torchilin).

Figure 4

Schematic representation of active targeting of a drug nanocarrier and uptake by tumour cells. (Reprinted with permission from reference [41]).

Figure 7

Main characteristics of mesoporous silica nanoparticles.

Figure 8

Schematic representation of the mesostructures of representative MSNs: (A) 2D hexagonal structures of MCM-41 and SBA-15 of the p6mm type. (Reprinted with permission from reference [74] Copyright © 2019 Licensee MDPI, Basel, Switzerland.) (B) Fragment of MCM-48 structure with la3d symmetry. (Reprinted with permission from reference [71].) (C) The 3D structure of the cubic-type Im3m SBA-16. (Reprinted with permission from references [78,80]. Copyright © 2016 International Journal of Pharmaceutical Investigation.)

Figure 9

The effect of particle size on the percentage of nanoparticles penetrating the mucous membrane. * and ** mean that a value is significantly different at p < 0.05 and p < 0.01, respectively, compared to other sizes. (Reprinted with permission from reference [105].)

Figure 10

A scheme depicting the formation of a multifunctional doxorubicin delivery system based on MSNs that is functionalized with folic acid (FA) as a target ligand, coated with a layer of gelatin blocking DOX inside mesopores, and additionally decorated with polyethylene glycol (PEG) to increase circulation time in the body. (Reprinted with permission from reference [115] with changes.)

Figure 11

Scheme for preparation of covalently cross-linked polymer shell via radical polymerisation of monomers. (Reprinted with permission from reference [116]. Copyright © 2011 American Chemical Society).

Figure 12

Schematic illustration of the synthesis strategy for organic functionalisation of MSNs. (Reprinted with permission from reference [122]. Copyright © 2019 World Scientific Publishing Company).

Figure 13

Stimuli controlling drug release from a nanocarrier. (Reprinted with permission from reference [126] with changes. Copyright © 2020 Licensee MDPI, Basel, Switzerland).

Figure 14

Preparation of pH-sensitive coated MSNs and drug release from nanocarriers. (Reprinted with permission from reference [133] with changes).

Figure 15

Illustration of the synthesis of redox-sensitive MSNs and drug release and disulfide cleavage. (Reprinted with permission from reference [156]. Copyright © 2012 American Chemical Society).