Formation of enzymatic/redox-switching nanogates on mesoporous silica nanoparticles for anticancer drug delivery

Wei Luo; Xin Xu; Bingjie Zhou; Peixin He; Yulin Li; Changsheng Liu

doi:10.1016/j.msec.2019.03.028

Formation of enzymatic/redox-switching nanogates on mesoporous silica nanoparticles for anticancer drug delivery

Mater Sci Eng C Mater Biol Appl. 2019 Jul:100:855-861. doi: 10.1016/j.msec.2019.03.028. Epub 2019 Mar 9.

Authors

Wei Luo¹, Xin Xu¹, Bingjie Zhou¹, Peixin He², Yulin Li³, Changsheng Liu⁴

Affiliations

¹ The Key Laboratory for Ultrafine Materials of Ministry of Education, State Key Laboratory of Bioreactor Engineering and Engineering Research Centre for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, China.
² Ministry-of-Education Key Laboratory for the Green Preparation and Application of Functional Materials, College of Chemistry and Chemical Engineering, Hubei University, Wuhan 430062, China.
³ The Key Laboratory for Ultrafine Materials of Ministry of Education, State Key Laboratory of Bioreactor Engineering and Engineering Research Centre for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, China. Electronic address: yulinli@ecust.edu.cn.
⁴ The Key Laboratory for Ultrafine Materials of Ministry of Education, State Key Laboratory of Bioreactor Engineering and Engineering Research Centre for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, China. Electronic address: liucs@ecust.edu.cn.

PMID: 30948123
DOI: 10.1016/j.msec.2019.03.028

Abstract

In this study, we demonstrate a simple approach to developing mesoporous nanohybrids via a process of pre-loading of an anticancer drug (doxorubicin, DOX) into mesoporous silica nanoparticles (MSN), followed by assembly with a kind of naturally-derived polymer (gelatin, cleavable by matrix metalloproteinase 2 overexpressed by tumor). The gelatin shell is then in situ crosslinked by degradable N,N'-bis(acryloyl)cystamine (BAC) to form enzymatic and redox switchable nanogates on the mesoporous nanoparticles. The nanohybrids displayed pH/redox/enzymatic sensitivity in DOX release under conditions mimicking tumor microenvironments. The nanocarriers can be effectively taken up by A549 cells (a carcinomic human alveolar basal epithelial cell line), resulting in a high DOX intracellular accumulation and an improved anticancer cytotoxicity when compared with free DOX, suggesting their potential as a nanoplatform for therapeutic delivery.

Keywords: Anticancer drug delivery; Gelatin; MMP 2 cleavable; Mesoporous nanoparticles; Nanogate.

MeSH terms

A549 Cells
Antineoplastic Agents / administration & dosage*
Cell Death / drug effects
Cell Survival / drug effects
Cystamine / chemistry
Doxorubicin / pharmacology
Drug Delivery Systems*
Drug Liberation
Enzymes / metabolism*
Humans
Nanoparticles / chemistry*
Nanoparticles / ultrastructure
Oxidation-Reduction
Porosity
Silicon Dioxide / chemistry*
Spectroscopy, Fourier Transform Infrared

Substances

Antineoplastic Agents
Enzymes
Silicon Dioxide
Doxorubicin
Cystamine