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 pretreated 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.

Redox-Responsive, Core-Cross-Linked Micelles Capable of On-Demand, Concurrent Drug Release and Structure Disassembly

“…29–31 Specific and rapid drug release at pathological sites could be potentially achieved using stimuli-responsive drug delivery system, minimizing the probability of drug resistance and systemic side effect. 32–34 Much effort has been devoted to the development of degradable micellar delivery systems that are responsive to intracellular changes of pH, 35–38 temperature, 39–41 glutathione (GSH) 38, 42–44 and enzyme level. 45–49 The large concentration gradient of GSH between the intracellular (~ 10 mM) and the extracellular environment (~ 0.002 mM) is an idea internal trigger for the design of redox-responsive micelles.…”

c(RGDyK)-decorated Pluronic micelles for enhanced doxorubicin and paclitaxel delivery to brain glioma

“…[5][6][7][8] The development of nanotechnology presents a promising approach for chemotherapeutics. Pluronic polymeric micelles, such as paclitaxel (PTX)-loaded vitamin E succinate-modified Pluronic micelles, 9 gold nanoparticle crosslinked PF-PTX-micelles, 10 17-AAG-loaded Pluronic P-123, F-127…”

Development of bimetallic (Zn@Au) nanoparticles as potential PET-imageable radiosensitizers

“…GNPs have been studied as sensitizers not only for radiotherapy but also for various other treatments, including thermal therapy 69 and chemotherapy. 70 Therefore, various GNP-mediated targeting and drug delivery methodologies have become available [71][72][73][74][75] and some of them are routinely used in laboratories. 76,77 The Zn@Au NPs that we developed have the same external structure as spherical GNPs and therefore have the potential to be used with the existing GNPmediated targeting methodologies.…”