title: Utilization of Enzyme-Immobilized Mesoporous Silica Nanocontainers (IBN-4) in Prodrug-Activated Cancer Theranostics.
abstract: To develop a carrier for use in enzyme prodrug therapy, Horseradish peroxidase (HRP) was immobilized onto mesoporous silica nanoparticles (IBN-4: Institute of Bioengineering and Nanotechnology), where the nanoparticle surfaces were functionalized with 3-aminopropyltrimethoxysilane and further conjugated with glutaraldehyde. Consequently, the enzymes could be stabilized in nanochannels through the formation of covalent imine bonds. This strategy was used to protect HRP from immune exclusion, degradation and denaturation under biological conditions. Furthermore, immobilization of HRP in the nanochannels of IBN-4 nanomaterials exhibited good functional stability upon repetitive use and long-term storage (60 days) at 4 °C. The generation of functionalized and HRP-immobilized nanomaterials was further verified using various characterization techniques. The possibility of using HRP-encapsulated IBN-4 materials in prodrug cancer therapy was also demonstrated by evaluating their ability to convert a prodrug (indole-3- acetic acid (IAA)) into cytotoxic radicals, which triggered tumor cell apoptosis in human colon carcinoma (HT-29 cell line) cells. A lactate dehydrogenase (LDH) assay revealed that cells could be exposed to the IBN-4 nanocomposites without damaging their membranes, confirming apoptotic cell death. In summary, we demonstrated the potential of utilizing large porous mesoporous silica nanomaterials (IBN-4) as enzyme carriers for prodrug therapy.
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien-974, Taiwan. baofungi@gmail.com.
authors.forename: Bau-Yen
authors.initials: BY
authors.lastname: Hung
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien-974, Taiwan. yaswanthk1987@gmail.com.
authors.forename: Yaswanth
authors.initials: Y
authors.lastname: Kuthati
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien-974, Taiwan. ranjithkankala@yahoo.com.
authors.forename: Ranjith Kumar
authors.initials: RK
authors.lastname: Kankala
authors.affiliation: Department of Chemistry, Kakatiya University, Telangana State-506009, India. shravankankala@yahoo.com.
authors.forename: Shravankumar
authors.initials: S
authors.lastname: Kankala
authors.affiliation: Department of Chemistry, Tamkang University, New Taipei City 251, Taiwan. jpdeng@mail.tku.edu.tw.
authors.forename: Jin-Pei
authors.initials: JP
authors.lastname: Deng
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien-974, Taiwan. cliu@mail.ndhu.edu.tw.
authors.forename: Chen-Lun
authors.initials: CL
authors.lastname: Liu
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien-974, Taiwan. chlee016@mail.ndhu.edu.tw.
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Lee
keywords: Institute of Bioengineering and Nanotechnology (IBN-4); anti-cancer; enzyme immobilization; mesoporous silica nanoparticles; prodrug therapy