Christophe Biot

@cbiot.bsky.social

Professor in Chemical Biology | Bridging chemistry and biology through innovation and collaboration

Glad to share our last studies in collaboration with Viktor Brabec. Photoactivatable Ir(III) Compound Penetrates the Blood-Brain Barrier in 3D Spheroidal and Advanced 3D Organoid Models of Inherently Resistant and Aggressive Brain Tumors | ACS Pharmacol & Transl Science pubs.acs.org/doi/full/10....

Photoactivatable Cyclometalated Ir(III) Compound Penetrates the Blood-Brain Barrier in 3D Spheroidal and Advanced 3D Organoid Models of Inherently Resistant and Aggressive Brain Tumors

The blood-brain barrier represents a significant challenge in delivering anticancer drugs for glioblastoma treatment. The study investigates the potential of a series of octahedral photoactivatable cyclometalated iridium complexes (Ir1–Ir10) with the general formula [Ir(ttpy)(C∧N)Cl]PF6 as photoactivated therapy candidates for the treatment of this aggressive tumor. These complexes, which include the terdentate ligand 4′-(p-tolyl)-2,2′:6′,2″-terpyridine (ttpy), and a C∧N ligand based on the deprotonated 2-arylbenzimidazole backbone, were tested on human glioblastoma using 2D cell cultures and 3D spheroidal models, including a fusion system comprising cerebral organoids from nonmalignant human-induced pluripotent stem cells and spheroids derived from malignant brain cells. The iridium complexes catalyze NADH photooxidation and photogenerate 1O2 and/or •OH under blue light irradiation. Blood-brain barrier penetration was assessed using various in vitro models. The complex Ir4, containing deprotonated methyl 1-butyl-2-phenylbenzimidazolecarboxylate, shows promise for targeted therapy of resistant brain tumors when photoactivated with blue light. Ir4 induces rapid and sustained ROS-mediated cytotoxicity and selectively accumulates in tumor tissue. This suggests its potential for fluorescently guided-PDT cooperative resection of glioblastoma. Notably, Ir4 significantly reduces glioblastoma growth even under dark conditions compared to conventional Temozolomide treatment without affecting healthy brain tissue.

pubs.acs.org

Happy to see the new paper from our great collaboration with @kargesgroup.bsky.social on #PDT, #Iridium and #HSA conjugation! Thanks to all-coauthors & also to @ruhr-uni-bochum.de, @UMU & @AEI

Karges Group@kargesgroup.bsky.social · last yr.

Check out our paper in @inorgchemfront.rsc.org about the Induction of Oncosis by Light Activation with an Ir(III) complex conjugated to Albumin. Congrats to Antonio, Zisis, and Lisa. Fantastic collaboration with @joseruizlab.bsky.social ! @ruhr-uni-bochum.de @um.es dx.doi.org/10.1039/D5QI...

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