Enzyme-/Redox-Responsive Mesoporous Silica Nanoparticles Based on Functionalized Dopamine as Nanocarriers for Cancer Therapy

Abstract

Mesoporous silica nanoparticles (MSNs) have been proved potential nanocarriers for efficient stimuli-triggered drug delivery systems (DDSs) in cancer therapy. We have developed a novel pepsin enzyme-responsive MSN based on mussel mimetic coating of dopamine for controlled release of drug delivery via a facile one-pot strategy. Herein, to improve drug release efficiency for cancer therapy, a novel dual-sensitive (enzyme- and redox-) MSN based on functionalized dopamine containing both peptide and disulfide bonds was designed and prepared. In detail, cystine-dopamine (Cy-DA) was newly synthesized and used as a monomer to self-polymerize into a coating on MSNs via simple a one-pot reaction to give rise to a chemotherapy drug [e.g., doxorubicin (DOX)] delivery system poly-Cy-DA-MSN. The in vitro cellular cytotoxicity tests of normal Marc-145 cells and HeLa cells showed that poly-Cy-DA-MSN was nontoxic, highly biocompatible, and suitable as drug carriers in controlled release DDS (CDDS). Because of the peptide and disulfide bonds in Cy-DA, the as-prepared DOX-loaded poly-Cy-DA-MSNs exhibited improving enzyme- and redox-responsive release property. Confocal laser scanning microscopy results showed that DOX@poly-Cy-DA-MSNs transported by the cells through endocytosis mechanism and the cancer drug DOX were released mainly in the cytoplasm and also in cell nucleus. These results showed that poly-Cy-DA-MSN is a promising double-responsive CDDS for sustained cancer therapy.