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

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Abstract

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 H2O2/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.

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Acknowledgements

The work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Ministry of Science and ICT, Korea (2021R1I1A3060098, NRF-2021R1I1A3059777 and Brain Korea 21 Plus Program (4199990414196)) and by the Korea Institute for Advancement of Technology funded by the Ministry of Trade, Industry and Energy (P0017531).

Funding

National Research Foundation of Korea, 2021R1I1A3060098,NRF-2021R1I1A3059777 and Brain Korea 21 Plus Program (4199990414196), Korea Institute for Advancement of Technology, P0017531

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  1. Wei-Jin Zhang and Amal Babu have contributed equally to this work.

Authors and Affiliations

  1. Department of Polymer Science and Engineering, School of Chemical Engineering, Pusan National University, Busan, 46241, Republic of Korea

    Wei-Jin Zhang, Yong-Zhu Yan, Nam-Ju Jo, Ildoo Chung, Suk-kyun Ahn & Chang-Sik Ha

  2. Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju, Republic of Korea

    Amal Babu & In-Kyu Park

  3. BioMedical Sciences Graduate Program (BMSGP), Chonnam National University, Hwasun, 58128, Republic of Korea

    Amal Babu & In-Kyu Park

  4. Division of Advanced Materials Engineering, Dong-Eui University, Busan, 47340, Republic of Korea

    Sung Soo Park

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WJZ carried out main experimental works and wrote the manuscript text, AB performed cell cytotoxicity experiments. SSP did project administration, YZY and NJ helped measurements and discussion. IC and SKA supervised this work, IKP helped interpreted biological data. CSH reviewed and edited this manuscript as well as supervised and got fund for this work. All authors read and approved the final manuscript.

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Zhang, WJ., Babu, A., Yan, YZ. et al. ROS/GSH dual-responsive selenium-containing mesoporous silica nanoparticles for drug delivery. J Porous Mater 30, 1469–1484 (2023). https://doi.org/10.1007/s10934-023-01430-6

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