Anticancer copper(II) phosphorus dendrimers are potent proapoptotic Bax activators

Mignani, Serge; Brahmi, Nabil El; Eloy, Laure; Poupon, Joël; Nicolas, Valérie; Steinmetz, Anke; Kazzouli, Saı̈d El; Bousmina, Mosto; Blanchard‐Desce, Mireille; Caminade, Anne‐Marie; Majoral, Jean‐Pierre; Cresteil, Thierry

doi:10.1016/j.ejmech.2017.03.035

Cited by 67 publications

(58 citation statements)

References 79 publications

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“…The free dendrimer moderately activates caspase-3, whereas the complex strikingly reduces the caspase-3 activity, and induces a noticeable translocation of Bax to the mitochondria, resulting in a severe DNA fragmentation. This is an original pathway for inducing apoptosis of cancer cells [87]. …”

Section: Optical Imagingmentioning

confidence: 99%

Recent therapeutic applications of the theranostic principle with dendrimers in oncology

et al. 2018

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Section: Optical Imagingmentioning

confidence: 99%

Recent therapeutic applications of the theranostic principle with dendrimers in oncology

et al. 2018

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“…The proteasome inhibitor MG132 reduces the degradation of ubiquitin-conjugated proteins by the 26S proteasome and activates c-Jun N-terminal kinase JNK1 [13]. Lastly, as reported previously, 1G3-Cu has been identified as an inducer of caspase-3-independent apoptosis via the translocation of Bax to mitochondria, promoting the release of AIF and finally the DNA fragmentation [8].…”

Section: Resultsmentioning

confidence: 71%

“…1G3-Cu demonstrated good antiproliferative potency against a panel of tumor cell lines with IC 50 s values ranging from 0.3 to 0.8 μM. Importantly, 1G3-Cu showed good cytotoxicity against cisplatin-resistant cell lines SK-OV3 and A2780/DDP [8]. Furthermore, we demonstrated that 1G3-Cu is a new first-in-class antiproliferative nanoparticle inducing apoptosis tumor cell death through the activation of Bax translocation and the caspase-independent apoptosis [8].…”

Section: Introductionmentioning

confidence: 96%

“…Importantly, 1G3-Cu showed good cytotoxicity against cisplatin-resistant cell lines SK-OV3 and A2780/DDP [8]. Furthermore, we demonstrated that 1G3-Cu is a new first-in-class antiproliferative nanoparticle inducing apoptosis tumor cell death through the activation of Bax translocation and the caspase-independent apoptosis [8]. Herein, we present the first investigation in the development of combination therapies associating the dendrimer 1G3-Cu with 5 cytotoxic agents used in chemotherapy having different modes of action.…”

Section: Introductionmentioning

confidence: 99%

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First-in-Class Combination Therapy of a Copper(II) Metallo-Phosphorus Dendrimer with Cytotoxic Agents

et al. 2018

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The metallo-phosphorus dendrimer 1G3-Cu (generation 3 dendrimer bearing 48 conjugated copper(II) on its surface) has antiproliferative activity related to its capacity to activate Bax translocation. In the present study, we evaluate the activity of an association of 1G3-Cu with 5 cytotoxic agents used in chemotherapy having different modes of action. Data show no additive effect with camptothecin and cisplatin, additivity with paclitaxel and MG132, and synergy with doxorubicin. Results suggest that the multivalent Cu-conjugated dendrimer 1G3-Cu (activator of Bax translocation) plays an important role in boosting the clinical impact of Bax accumulation stimulated by the proteasome inhibitor MG132, antimitotic taxanes, and the topo II inhibitor doxorubicin.

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“…Dendrimers due to their proper, reproducible, and optimized design parameters overcoming the physicochemical limitations of classical drugs (for example, solubility, specificity, stability, biodistribution, and therapeutic efficiency) are successful. They are also able to omit biological problems to reach the right targets such as firstpass effect, immune clearance, cell penetration, and off-target interactions [27]. Polymers are commonly used materials for nanoparticles-based delivery [28], among them dendrimers are the ones more commonly used as a non-viral delivery system.…”

Section: Dendrimers As Drug Delivery Systemsmentioning

confidence: 99%

Dendrimers as Drug Nanocarriers: The Future of Gene Therapy and Targeted Therapies in Cancer

Franiak-Pietryga¹,

Ziemba²,

Messmer³

et al. 2018

Dendrimers - Fundamentals and Applications

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Synthetic polymers, such as dendrimers, play a critical role in pharmaceutical discovery and development. Advances in the application of nanotechnology in medicine have given rise to multifunctional "smart" nanocarriers that can deliver one or more therapeutic agents safely and selectively to cancer cells, including intracellular gene-specific targeting. Dendrimers with their 3D nanopolymeric architectures are highly attractive class of drug and gene delivery vector. Advances in understanding and manipulating genes gave scientists a tool to make changes in people DNA to prevent or treat diseases. Over the past decade, gene therapy has been in use in clinical trials. The inactivation of the tumor suppressor genes is the main idea of the development of gene therapy in the cancer treatment. Broad spectrum of delivery concepts, including viral vectors, liposomes, cationic polymers and dendrimers, cell-penetrating peptides and gold and magnetic nanoparticles have been investigated. A well-designed vector is the most desirable approach to increase the safety of gene therapy, which is still in its infancy stages in cancer research. More experimental and clinical trials are focused on well-designed and effective doses of vectors that are essential for therapeutic efficacy of gene therapy for its potential in clinical use against a wide variety of cancers.

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Anticancer copper(II) phosphorus dendrimers are potent proapoptotic Bax activators

Cited by 67 publications

References 79 publications

Recent therapeutic applications of the theranostic principle with dendrimers in oncology

Recent therapeutic applications of the theranostic principle with dendrimers in oncology

First-in-Class Combination Therapy of a Copper(II) Metallo-Phosphorus Dendrimer with Cytotoxic Agents

Dendrimers as Drug Nanocarriers: The Future of Gene Therapy and Targeted Therapies in Cancer

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