Biomolecular-Responsive Drug Release from Mesoporous Silica Nanoparticles

Biomolecules like enzymes, glucose, aptamers, and antigens are most commonly used to prompt drug release (Schlossbauer et al.,

SERS-positive mesoporous silica nanomaterial for cancer theranostics

FIGURE 3.5 SERS-positive mesoporous silica nanomaterial for cancer theranostics.

List of Diverse Strategies Employed for pH-Responsive Mesoporous Silica Nanoparticle-Based Delivery Systems with Different Functionalities


Hyaluronidase-Responsive Mesoporous Silica Nanoparticles

Other Modifications

Therapeutic Agents


Polyelectrolyte Multilayers Poly Allylamine hydrochloride and Sodium Poly (Styrene Sulfonata)


Feng et al. (2013)

Cerium Oxide Nanoparticles and PDEAEMA

Hematoporphyrin (HP) for NIR light responsive


Wenet al. (2016)


AuNPs for NIR Irradiation and Magnetite (Fe,04) NPs for AMF responsive


Liu et al. (2019)


p-anisidino linkers

Propidium Iodide

Du et al. (2012)

Polyacrylic Acid

Fe,0 ; NPs core


Wu et al. (2012)


PEG along with a-CD


Gao et al. (2012)

Carboxylate functional group

Janus Ag-mesoporous silica nanoparticles for SERS activity


Shao et al. (2016)

2009). Biomolecules give a quick response to internal changes and body stimuli. Atypical enzymatic activities are generally observed in tissues involved in pathological conditions. These conditions and responses could be targeted using enzyme-stimulated nano-gates that help in blocking the mesopores of mesoporous silica nanoparticles, thereby aiding in a sustained drug release. In a typical strategic design, mesoporous silica nanoparticles loaded with [Ru(bipy)3]2+ dye and capped with antibodies have shown the potential to regulate the opening and closing of nanotunnels present in mesoporous silica nanoparticles when exposed to specific antigens like sulfathiazole (Climent et al., 2009). In order to achieve this regulation, the surface of mesoporous silica nanoparticles was functionalized with the help of (4-(4-aminobenzenesulfonylamino) benzoic acid, a class of haptens, which could be easily recognized by a specific antibody. The haptens bind to the antigen-binding sites of the antibody, which in turn is capped to the surface of mesoporous silica nanoparticles. On exposure of antibody-capped mesoporous silica nanoparticles to specific antigen sulfathiazole, the antibody incorporated on the surface of mesoporous silica nanoparticles, due to its antigen specificity binds to the antigen and thereby gets dislocated from mesoporous silica nanoparticles. This results in the release of cargo loaded inside the pores of mesoporous silica nanoparticles.

In another strategy, nucleic acid aptamers were used to cap the pores of mesoporous silica nanoparticles and the advantage of the target specificity of aptamers were explored to achieve an effective stimuli-responsive drug release system (Chun-Ling Zhu et al., 2011). Aptamers are single-stranded short oligonucleotide sequences with high specificity to particular targets. Stability and biodegradability, being less prone to denaturation, easy to obtain, and simplicity for modification are some advantages associated with aptamers when compared to an antibody, making them a potent choice for aiding in drug delivery strategies. An aptamer-mediated mesoporous silica nanoparticles delivery system was designed with the pores of mesoporous silica nanoparticles capped with adenosine triphosphateaptamer tagged with gold nanoparticles. When exposed to a pathological environment associated with cancer cells, the increased adenosine triphosphate production in cancer cells displaces the aptamer-tagged gold nanoparticles, thereby allowing release of the cargo molecule loaded in the mesopores of mesoporous silica nanoparticles. A list of recently used biomolecules to functionalize the mesoporous silica nanoparticles for the therapeutic delivery in cancer has been provided in Table 3.2. Hyaluronidase-Responsive

Mesoporous Silica Nanoparticles

Zhang et al.’s work (2019) led to the construction of hybrid mesoporous silica nanoparticles with responsive ability towards intracellular stimuli of glutathione and hyaluronidase. Thesemesoporous silica nanoparticles were functionalized with hyaluronic acid and polyethyleneimine for co-delivery of bcl-2 siRNA and doxorubicin. Apart from conventional techniques for mesoporous silica nanoparticle fabrication, a biodegradable hybrid mesoporous silica nanoparticle was also synthesized from tetraethyl orthosilicate and bis[3-(triethoxysilyl)propyl]


List of Biomolecule-Functionalized Mesoporous Silica Nanoparticle-Based Delivery Systems


Other Modifications

Therapeutic Agents


(4-(4-aminobenzenesulfonylamino) benzoic acid,


[Ru(bipy)3]2+ dye

Climent et al. (2009)

Nucleic Acid Aptamers

Adenosine triphosphate and gold nanoparticles

Fluorescein dye

Chun-Ling Zhu et al. (2011)

Hyaluronic acid


bcl-2 siRNA and Doxorubicin

Zhang et al. (2019)

Hyaluronic acid

Desthiobiotin-streptavidin complex


Zhang et al. (2016)


Poly A (Adenine) tail


Li et al. (2019)

tetrasulfide. Cetyltrimethylammonium chloride and triethanolamine were reacted at 95°C, followed by addition of tetraethyl orthosilicate to form a core layer of mesoporous silica nanoparticles, then a mixed solution of tetraethyl orthosilicate and bis[3- (triethoxysilyl)propyl] tetrasulfide was used to create the outer hybrid layer of hollow-mesoporous silica nanoparticles. The collected hollow-mesoporous silica nanoparticles were transformed into hollow-mesoporous silica nanoparticles/hyaluronic acid/ polyethyleneimine for the designated application, and conjugation of hyaluronic acid and polyethyleneimine was achieved by the ionic adsorption method before loading the doxorubicin and bcl-2 siRNA. The nanocarriers were sensitive to glutathione which could cleave the disulphide bridges and lead to degradation of the hybrid mesoporous silica nanoparticles as confirmed by the irregular shapes of the nanoparticles when kept in the presence of glutathione for 14 days. Moreover, these systems were responsive to hyaluronidase due to the presence of its substrate, hyaluronic acid in the nanoparticles (Zhang et al., 2019). In addition, the doxorubicin release was very sensitive to the presence of glutathione and hyaluronidase at pH of (7.4 and 5). The presence of the upregulated conditions of CD44 and biotin in cancer could be utilized for the targeted therapeutics. The CD44 receptor helps the internalization of hyaluronic acid through receptor-mediated endocytosis, and hyaluronidase degrades hyaluronic acid used as an enzyme substrate. Biotin binds specifically to streptavidin and a modified form of biotin, desthiobiotin, less tightly binds to streptavidin but with an efficient binding specificity. A study conducted by Zhang et al. established a mesoporous dual responsive drug delivery of doxorubicin for colon cancer using intracellular hyaluronidase and a biotin-streptavidin complex as gatekeepers. The fabrication of this nano-system initiated with the modification of mesoporous silica nanoparticles-NH, on the external surface of mesoporous silica nanoparticles with N-Hydroxysuccinimide-desthiobiotin to make desthiobiotin-mesoporous silica nanoparticles, followed by the blocking of pores with streptavidin using the desthiobio- tin-streptavidin interaction. Also, the pores were blocked by the biotin modified hyaluronic acid to achieve the tumor targeting (Zhang et al., 2016).

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