Amino-functionalized nanoparticles as inhibitors of mTOR and inducers of cell cycle arrest in leukemia cells

Biomaterials
Cornelia LoosThomas Simmet

Abstract

Activation of the mammalian target of rapamycin (mTOR) has been implicated in anticancer drug resistance, type 2 diabetes, and aging. Here, we show that surface functionalization of polystyrene nanoparticles with amino groups (PS-NH2), but not with carboxyl groups (PS-COOH), induces G2 cell-cycle arrest and inhibition of proliferation in three leukemia cell lines. Besides, PS-NH2 inhibit angiogenesis and proliferation of leukemia cells xenografted onto the chick chorioallantoic membrane. At the molecular level, PS-NH2 inhibit, whereas PS-COOH activate mTOR signaling in leukemia cells. Consistently, PS-NH2 block activation of the mTOR downstream targets, Akt and p70 ribosomal S6 kinase 1, and induce overexpression of the cell-cycle regulator p21(Cip1/Waf1) and degradation of cyclin B1. After addition, both types of particles rapidly induce autophagy in leukemia cells. Yet, only in PS-NH2-treated cells, acidic vesicular organelles show elevated pH and impaired processing of procathepsin B. Moreover, solely in PS-NH2-treated cells, autophagy is followed by permeabilization of acidic vesicular organelles and induction of apoptosis. By contrast, primary macrophages, which do not exhibit activated mTOR signaling, proved relatively re...Continue Reading

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Citations

Feb 24, 2016·Trends in Biotechnology·Laura HuleaVladimir Trajkovic
Dec 25, 2015·ACS Applied Materials & Interfaces·Can HuangYourong Duan
Sep 5, 2015·Current Opinion in Biotechnology·Lauren Popp, Laura Segatori
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Oct 16, 2014·The Journal of Pharmacology and Experimental Therapeutics·Menna El GaafaryThomas Simmet
Aug 15, 2019·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Christian SecaCiro Isidoro
Feb 12, 2015·Beilstein Journal of Nanotechnology·Cornelia LoosThomas Simmet
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Dec 1, 2017·Journal of Natural Products·Menna El GaafaryThomas Simmet

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