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WIREs Nanomed Nanobiotechnol
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Metal‐based phosphorus dendrimers as novel nanotherapeutic strategies to tackle cancers: A concise overview

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Abstract Several metal‐based phosphorus dendrimers were prepared. The first series developed by us was the Cu(II) series. In this series, the most potent is the third generation‐Cu(II) showing original mechanism of action with activation of the pro‐apoptotic Bax protein. To our knowledge, it is the first example of nanoparticles displaying Bax protein activation and then cell death through apoptosis process. Interestingly, this dendritic‐Cu(II) complex showed synergistic effect with doxorubicin. Based on these interesting anti‐proliferative activities, we developed Au(III)‐conjugated phosphorus dendrimers. The most potent is the third generation‐Au(III) dendrimer which represents also a new and promising first‐in‐class anti‐proliferative agent against both solid and liquid tumor cell lines. Then, in order to analyze the influence of the metal moiety distribution of Cu(II) and Au(III) on the surface of dendrimers, mix Cu(II)–Au(III)‐conjugated phosphorus dendrimers were also prepared and tested as anti‐proliferative agents. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Two‐dimensional chemical structure of phosphorus dendrimers
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Chemical structure of several metallo‐based pharmaceuticals
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Two‐dimensional schematic general structure of multivalent phosphorus dendrimers prepared
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Two‐dimensional chemical structure of plain 1G3 and 1G3‐Cu dendrimers
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Growth inhibition effects of 1G3 and 1G3‐Cu upon a panel of tumor cells and normal cells. Data are expressed as the mean ± SE of IC50 calculated for two individual determinations in duplicate. *p < .05, **p < .01
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Two‐dimensional chemical structure of 1G3‐Cu(II), 1G3‐Au(III), and 1G3‐Fe(II) dendrimers
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Metal moiety distribution of phosphorus 1G3 dendrimers. Gray color corresponds to the complexation of the bidentate chelator N‐(pyridin‐2‐ylmethylene)ethanamine (NN) grafted on the G3 phosphorus dendrimers and complexed with Cu(II) metal; blue corresponds to the N‐(pyridin‐2‐ylmethylene) ethanamine (NN) grafted on the G3 phosphorus dendrimer without Cu(II); yellow color corresponds to the PEG chain (11 CH2CH2O linkages) grafted on the G3 phosphorus dendrimers; the yellow color corresponds to the bidentate chelator N‐(pyridin‐2‐ylmethylene)ethanamine (NN) grafted on the G3 phosphorus dendrimers and complexed with Au(III) metal
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Schematic representation of the mechanism of action of 1G3 and 1G3‐Cu
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Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

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