Glutathione-sensitive Hollow Mesoporous Silica Nanoparticles For Controlled Drug Delivery

Abstract

Tunable glutathione (GSH)-sensitive hollow mesoporous silica nanoparticles (HMSiO 2 NPs) were developed using a structural difference-based selective etching strategy. These organosilica hollow nanoparticles contained disulfide linkages (S-S) in the outer shell which were degraded by GSH. The particles were compared with their nonGSH-sensitive tetraethyl orthosilicate (TEOS) HMSiO 2 counterparts in terms of their synthesis method, characterization, doxorubicin (DOX) release profile, and in vitro cytotoxicity in MCF-7 breast cancer cells. Transmission electron microscopy (TEM) of the particles indicated that the fabricated HMSiO 2 NPs had an average diameter of 130 ± 5 nm. Thermogravimetric analysis (TGA) revealed that GSH-sensitive particles had approximately 5.3% more weight loss than TEOS HMSiO 2 NPs. Zeta potential of these redox-responsive particles was −23 ± 1 mV at pH 6 in deionized (DI) water. Nitrogen adsorption-desorption isotherm revealed that the surface area of the hollow mesoporous nanoreservoirs was roughly 446 ± 6 m 2 g −1 and the average diameter of the pores was 2.3 ± 0.5 nm. TEM images suggest that the nanoparticles started to lose mass integrity from Day 1. The particles showed a high loading capacity for DOX (8.9 ± 0.5%) as a model drug, due to the large voids existing in the hollow structures. Approximately 58% of the incorporated DOX released within 14 days in phosphate buffered saline (PBS) at pH 6 and in the presence of 10 mM of GSH, mimicking intracellular tumor microenvironment while release from TEOS HMSiO 2 NPs was only c.a. 18%. The uptake of these hollow nanospheres by MCF-7 cells and RAW 264.7 macrophages was evaluated using TEM and confocal microscopy. The nanospheres were shown to accumulate in the endolysosomal compartments after incubation for 24 h with the maximum uptake of c.a. 2.1 ± 0.3% and 5.2 ± 0.4%, respectively. Cytotoxicity of the nanospheres was investigated using CCK-8 assay. Results indicate that intact hollow particles (both GSH-sensitive and TEOS HMSiO 2 NPs) were nontoxic to MCF-7 cells after incubation for 24 h within the concentration range of 0–1000 μg ml −1 . DOX-loaded GSH-sensitive nanospheres containing 6 μg ml −1 of DOX killed c.a. 51% of MCF-7 cells after 24 h while TEOS HMSiO 2 NPs killed c.a. 20% with the difference being statistically significant. Finally, cytotoxicity data in RAW 264.7 macrophages and NIH 3 T3 fibroblasts shows that intact GSH-sensitive HMSiO 2 NPs did not show any toxic effects on these cells with the concentrations equal or <125 μg ml −1 .

Department(s)

Chemical and Biochemical Engineering

Comments

National Science Foundation, Grant DMR-1121252

Keywords and Phrases

Degradable; GSH-sensitive; High loading capacity; Hollow mesoporous silica nanoparticles; Structural difference; Tunable

International Standard Serial Number (ISSN)

1873-4995; 0168-3659

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2025 Elsevier, All rights reserved.

Publication Date

28 Jul 2018

PubMed ID

29679666

Link to Full Text

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