Fe-doped mesoporous silica catalyzes ascorbic acid oxidation for tumor-specific therapy in scaffold

Cijun Shuai; Xuan Chen; Chongxian He; Min Chen; Shuping Peng; Wenjing Yang

doi:10.1016/j.colsurfb.2023.113251

Fe-doped mesoporous silica catalyzes ascorbic acid oxidation for tumor-specific therapy in scaffold

Colloids Surf B Biointerfaces. 2023 May:225:113251. doi: 10.1016/j.colsurfb.2023.113251. Epub 2023 Mar 7.

Authors

Cijun Shuai¹, Xuan Chen², Chongxian He³, Min Chen², Shuping Peng⁴, Wenjing Yang⁵

Affiliations

¹ Institute of Additive Manufacturing, Jiangxi University of Science and Technology, Nanchang 330013, China; State Key Laboratory of High Performance Complex Manufacturing, Central South University, Changsha 410083, China; Shenzhen Institute of Information Technology, School of Sino-German Robotics, Shenzhen 518115, China.
² Institute of Additive Manufacturing, Jiangxi University of Science and Technology, Nanchang 330013, China.
³ State Key Laboratory of High Performance Complex Manufacturing, Central South University, Changsha 410083, China.
⁴ The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha 410078, China; NHC Key Laboratory of Carcinogenesis of Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha 410013, China; School of Energy and Machinery Engineering, Jiangxi University of Science and Technology, Nanchang 330013, China. Electronic address: shuping@csu.edu.cn.
⁵ Institute of Additive Manufacturing, Jiangxi University of Science and Technology, Nanchang 330013, China. Electronic address: yangwenjing@jxust.edu.cn.

PMID: 36931045
DOI: 10.1016/j.colsurfb.2023.113251

Abstract

Ascorbic acid (AA) is a promising antitumor agent, yet its autooxidation is too slow which constrains the further application. Fortunately, the autoxidation process can be accelerated by transition metal catalysts, especially Fe³⁺ ions. In this study, AA was loaded to Fe-doped mesoporous silica (designated as AA@Fe-SiO₂), which was introduced into poly-L-lactic acid (PLLA) and then prepared into a scaffold. Mechanistically, AA@Fe-SiO₂ degraded in acidic tumor microenvironment because excessive H⁺ substituted Fe atoms in the iron silicate framework, releasing Fe³⁺ and AA. The Fe³⁺ boosted the pro-oxidation reaction of AA, generating numerous hydrogen peroxide (H₂O₂) and Fe²⁺. Then, Fe²⁺ reacted with H₂O₂ to initiate Fenton reactions favoring hydroxyl radical generation, triggering oxidative damage on tumor cells to implement tumor-specific therapy. Results showed that the release amount of AA in acidic solution was about 3 times higher than that in neutral solution, which was attributed to the pH-dependency of the degradation of AA@Fe-SiO₂ in scaffold. Furthermore, the scaffold generated numerous ascorbate radical intermediate and increased the H₂O₂ concentration by 120.2%, demonstrating that Fe³⁺ remarkably accelerated the oxidation rate of AA. Cell experimental results showed that the scaffold caused massive apoptosis of tumor cells, while no obvious cytotoxicity to normal cells, confirming the antitumor specificity of scaffold. This work paves a promising way to construct a biodegradable and catalytic scaffold, featuring effective tumor-specific therapy.

Keywords: Ascorbic acid; Pro-oxidation; Scaffold; Tumor-specific therapy.

MeSH terms

Acids
Ascorbic Acid*
Hydrogen Peroxide / metabolism
Iron
Oxidation-Reduction
Silicon Dioxide*

Substances

Ascorbic Acid
Silicon Dioxide
Hydrogen Peroxide
Iron
Acids