Bypassing the Resistance Mechanisms of the Tumor Ecosystem by Targeting the Endoplasmic Reticulum Stress Pathway Using Ruthenium-and Osmium-Based Organometallic Compounds: An Exciting Long-Term Collaboration with Dr. Michel Pfeffer

Metal complexes have been used to treat cancer since the discovery of cisplatin and its interaction with DNA in the 1960’s. Facing the resistance mechanisms against platinum salts and their side effects, safer therapeutic approaches have been sought through other metals, including ruthenium. In the early 2000s, Michel Pfeffer and his collaborators started to investigate the biological activity of organo-ruthenium/osmium complexes, demonstrating their ability to interfere with the activity of purified redox enzymes. Then, they discovered that these organo-ruthenium/osmium complexes could act independently of DNA damage and bypass the requirement for the tumor suppressor gene TP53 to induce the endoplasmic reticulum (ER) stress pathway, which is an original cell death pathway. They showed that other types of ruthenium complexes—as well complexes with other metals (osmium, iron, platinum)—can induce this pathway as well. They also demonstrated that ruthenium complexes accumulate in the ER after entering the cell using passive and active mechanisms. These particular physico-chemical properties of the organometallic complexes designed by Dr. Pfeffer contribute to their ability to reduce tumor growth and angiogenesis. Taken together, the pioneering work of Dr. Michel Pfeffer over his career provides us with a legacy that we have yet to fully embrace.

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Concentration Effect over Thermoresponse Derived from Organometallic Compounds of Functionalized Poly(N-isopropylacrylamide-co-dopamine Methacrylamide)

Polymers ◽

10.3390/polym13223921 ◽

2021 ◽

Vol 13 (22) ◽

pp. 3921

Author(s):

María Moral-Zamorano ◽

Isabel Quijada-Garrido ◽

Verónica San-Miguel ◽

Berna Serrano ◽

Juan Baselga ◽

...

Keyword(s):

Hydrophobic Interactions ◽

Chemical Properties ◽

Organometallic Compounds ◽

Drug Carriers ◽

Organometallic Complexes ◽

Concentration Effect ◽

Solution Temperature ◽

Organometallic Complex ◽

Vis Spectroscopy ◽

Clear Idea

The functionalization of smart polymers is opening a new perspective in catalysis, drug carriers and biosensors, due to the fact that they can modulate the response regarding conventional devices. This smart response could be affected by the presence of organometallic complexes in terms of interactions which could affect the physical chemical properties. In this sense, the thermoresponsive behavior of copolymers based on N-isopropylacrylamide (NIPAM) could be affected due to the presence of hydrophobic groups and concentration effect. In this work, the functionalization of a copolymer based on NIPAM and dopamine methacrylamide with different amounts of bis(cyclopentadienyl)titanium (IV) dichloride was carried out. The resulting materials were characterized, showing a clear idea about the mechanism of functionalization through FTIR spectroscopy. The thermoresponsive behavior was also studied for various polymeric solutions in water by UV–vis spectroscopy and calorimetry. The hydrophobic interactions promoted by the organometallic complex could affect the transition associated with the lower critical solution temperature (LCST), specifically, the segments composed by pure NIPAM. That fact would explain the reduction of the width of the LCST-transition, contrary to what could be expected. In addition, the hydrophobicity was tested by the contact angle and also DNA interactions.

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