Details

Autor(en) / Beteiligte

• Chen, Wei-liang
• Yang, Shu-di
• Li, Fang
• Qu, Chen-xi
• Liu, Yang
• Wang, Yu
• Wang, Dan-dan
• Zhang, Xue-nong

Titel

Programmed pH/reduction-responsive nanoparticles for efficient delivery of antitumor agents in vivo

Ist Teil von

• Acta biomaterialia, 2018-11, Vol.81, p.219-230

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2018

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• [Display omitted] To bypass the biological barriers during the drug delivery process, it is desirable to develop smart nanoparticles (NPs) with flexible physical and chemical properties. In this study, a programmed NP delivery system with a pH-triggered detachable PEG layer and a lactobionic acid (Lac)-modified reduction-responsive core was developed to address the “PEG dilemma” and provide an on-demand intracellular release of doxorubicin (DOX). The positively charged DOX-loaded lactobionic acid-chitosan-lipoic acid (DOX/LCL) NPs were prepared and coated with a negatively charged dimethylmaleic acid-PEG-chitosan (PEG-CS-DA) layer to obtain a prolonged circulation time and improve the tumor-targeting effect. After reaching the tumor tissues through a targeted delivery effect, the surface charge of the PEG-CS-DA layer was reversed from negative to positive because of the trigger by the acidic microenvironment (pH 6.8), thus leading to the detachment of the PEG layer. The exposure of positive charges and the active targeting ligand enhanced cellular uptake and facilitated penetration into tumor tissues. Subsequently, the rapid release and diffusion of DOX into the nuclei was triggered by the intracellular high concentration of glutathione, thus leading to cell apoptosis. In conclusion, these programmed pH/reduction-responsive NPs provide a promising strategy for the delivery of antitumor agents in vivo. In this study, novel programmed pH/reduction-responsive NPs were developed for the delivery of DOX in vivo. These NPs were coated with a negatively charged PEG layer to improve the serum stability and tumor target effect. The PEG layer detached because of the trigger by tumor acidic microenvironment (pH 6.8), thus leading to the exposure of positive charges and the active targeting ligand, which enhanced cellular uptake and facilitated penetration into tumor tissues. Subsequently, the rapid release of DOX was triggered by the intracellular high concentration of glutathione, thereby resulting in enhanced cytotoxicity. These programmed pH/reduction-responsive NPs provide a promising strategy for the delivery of antitumor agents in vivo.