Reduction-responsive gold-nanoparticle-conjugated Pluronic micelles: an effective anti-cancer drug delivery system

Abstract

In this study, gold-nanoparticle-crosslinked Pluronic micelles were synthesized and used as a carrier for paclitaxel (PTX). The resultant PTX-loaded gold-nanoparticle-crosslinked Pluronic micelles were about 69 nm in diameter. Physical stability and in vivo pharmacokinetic studies revealed that these micelles were more stable as compared to the non-cross-linked controls. Fluorescence microscopy and flow cytometry analyses showed that PTX-loaded cross-linked micelles had excellent cellular uptake ability by human glioma U87 cells. The cleavage of disulfide bridge linkages under glutathione stimulus resulted in destruction of micelles and induced rapid drug release. In vitro cytotoxicity studies revealed that these cross-linked micelles exhibited high anti-cancer activity against glutathione monoester pre-treated U87 cells compared to non-pretreated cells. Cytoarchitecture studies demonstrated a similar cytoskeleton pattern before and after cross-linked micelles loaded into bone marrow derived macrophages. In vivo fresh frozen sections showed that cross-linked micelles were preferably accumulated in spleen and liver. These results indicated that gold-nanoparticle-crosslinked Pluronic micelles can be used as potential anti-cancer drug carriers for intelligent drug delivery.