ROS/GSH dual-responsive selenium-containing mesoporous silica nanoparticles for drug delivery

• Published in: Journal of porous materials Vol. 30; no. 5; pp. 1469 - 1484
• Main Authors: Zhang, Wei-Jin, Babu, Amal, Yan, Yong-Zhu, Park, Sung Soo, Jo, Nam-Ju, Chung, Ildoo, Ahn, Suk-kyun, Park, In-Kyu, Ha, Chang-Sik
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2023; Springer Nature B.V
• Subjects: Aminopropyltriethoxysilane; Biocompatibility; Catalysis; Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Drug carriers; Drug delivery systems; Functional groups; Glutathione; Hydrogen peroxide; In vivo methods and tests; Nanoparticles; Oxidation; Performance evaluation; Physical Chemistry; Polyethyleneimine; Reagents; Reducing agents; Scanning microscopy; Selenium; Silicon dioxide; Cell viability; Chemotherapy; Mesoporous silica; Redox-responsive; Fluorouracil
• ISSN: 1380-2224; 1573-4854
• DOI: 10.1007/s10934-023-01430-6

The targeted delivery of anti-tumor drugs to diseased sites is significant in cancer therapy. Herein, a novel redox-responsive 5-fluorouracil (5-FU) prodrug delivery system based on mesoporous silica nanoparticles was proposed, in which polyethyleneimine (PEI, a bulky gatekeeper) and (3-aminopropyl) triethoxysilane-functionalized MCM41 were conjugated to an identical 3,3-diselanediyldipropionic acid linker via a condensation reaction between the amino group and carboxyl functional group. The chemotherapeutic reagent 5-FU was filled into the pores of Se-MCM41 nanocarriers as a model drug. The nanoparticles of PEI-Se-MCM41@5-FU exhibited a uniform and spherical morphology of approximately 175 nm. Under high concentrations of reactive oxygen species or glutathione (GSH) environments, such as the tumor microenvironment, 5-FU was rapidly released from the PEI-Se-MCM41 nanocarrier owing to its high sensitivity to both oxidizing and reducing agents. The release performance clearly verified the feasibility of PEI-Se-MCM41@5-FU nanoparticles for H 2 O 2 /GSH-triggered 5-FU release, particularly under GSH conditions. Additionally, the cytotoxic effects of PEI-Se-MCM41 nanoparticles findings indicating that there was no significant cytotoxicity against CT-26 colon cancer cells after 24 h incubation. However, PEI-Se-MCM41@5-FU nanoparticles exhibited a pronounced inhibitory effect on CT-26 cells at a concentration of 150 μg mL −1 . Furthermore, the intracellular drug delivery performance of nanocarriers were evaluated using confocal laser scanning microscopy (CLSM), which disclosed that the PEI-Se-MCM41@RhB was successfully endocytosed into the CT-26 cells and released the loaded 5-FU. The conclusion was further proved by FACS analysis, which indicated that PEI-Se-MCM41@RhB was more easily uptaken into the CT-26 cells than free RhB. The findings of in vivo and in vitro studies suggest that PEI-Se-MCM41@5-FU holds great potential for effective tumor therapy.