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.

Nanoparticles containing mixed lipid monolayer shell, biodegradable polymer core and rabies virus glycoprotein (RVG) peptide as brain targeting ligand, were developed for brain targeted delivery of paclitaxel (PTX) to treat malignant glioma. RVG conjugated PTX loaded NPs (RVG-PTX-NPs) had the desirable size (~140 nm), narrow size distribution and spherical shape. RVG-PTX-NPs showed poor uptake by neurons and selective targeting to the brain tumor associated macrophages (TAMs) with controlled release and tumor specific toxicity. In vivo studies revealed that RVG-PTX-NPs were significant to cross the blood-brain barrier (BBB) and had specific targeting to the brain. Most importantly, RVG-PTX-NPs showed effectiveness for anti-glioma therapy on human glioma of mice model. We concluded that RVG-PTX-NPs provided an effective approach for brain-TAMs targeted delivery for the treatment of glioma.

Interleukin-27 (IL-27) is a cytokine that suppresses human immunodeficiency virus (HIV)-1 infection in macrophages and is considered as an immunotherapeutic reagent for infectious diseases. It is reported that IL-27 suppresses autophagy in Mycobacterium tuberculosis-infected macrophages; however, a role for IL-27 on autophagy induction has been less studied. In this study, we investigated the impact of IL-27 in both autophagy induction and HIV-1 infection in macrophages. Primary human monocytes were differentiated into macrophages using human AB serum (huAB) alone, macrophage-colony stimulating factor (M-CSF) alone, or a combination of IL-27 with huAB or M-CSF. Electron microscopy and immunofluorescence staining demonstrated that a 20-fold increase in autophagosome formation was only detected in IL-27 + huAB-induced macrophages. Western blot analysis indicated that the autophagosome induction was not linked to either dephosphorylation of the mammalian target of rapamycin (mTOR) or lipidation of microtubule-associated protein 1A/1B-light chain 3 (LC3), an autophagosomal marker, implying that IL-27 can induce autophagy through a novel non-canonical pathway. Here we show for the first time that IL-27 induces autophagy during monocyte-to-macrophage differentiation in a subtype-dependent manner.