10.1021\/jacs.3c04855<\/a><\/p>\nAuthors:<\/h4>\n
Liyan Zhang, Peiyuan Wang, Xue\u2010Quan Zhou, Ludovic Bretin, Xiaolong Zeng, Yurii Husiev, Ehider A. Polanco, Gangyin Zhao, Lukas S. Wijaya, Tarita Biver, Sylvia E. Le D\u00e9v\u00e9dec, Wen Sun, Sylvestre Bonnet<\/p>\n
Abstract:<\/h4>\n
To investigate the potential of tumor-targeting photoactivated chemotherapy, a chiral ruthenium-based anticancer warhead, \u039b\/\u0394-[Ru(Ph2<\/sub>phen)2<\/sub>(OH2<\/sub>)2<\/sub>]2+<\/sup>, was conjugated to the RGD-containing Ac-MRGDH-NH2<\/sub> peptide by direct coordination of the M and H residues to the metal. This design afforded two diastereoisomers of a cyclic metallopeptide, \u039b-[1<\/b>]Cl2<\/sub> and \u0394-[1<\/b>]Cl2<\/sub>. In the dark, the ruthenium-chelating peptide had a triple action. First, it prevented other biomolecules from coordinating with the metal center. Second, its hydrophilicity made [1<\/b>]Cl2<\/sub> amphiphilic so that it self-assembled in culture medium into nanoparticles. Third, it acted as a tumor-targeting motif by strongly binding to the integrin (K<\/i>d<\/sub> = 0.061 \u03bcM for the binding of \u039b-[1<\/b>]Cl2<\/sub> to \u03b1IIb<\/sub>\u03b23<\/sub>), which resulted in the receptor-mediated uptake of the conjugate in vitro<\/i>. Phototoxicity studies in two-dimensional (2D) monolayers of A549, U87MG, and PC-3 human cancer cell lines and U87MG three-dimensional (3D) tumor spheroids showed that the two isomers of [1<\/b>]Cl2<\/sub> were strongly phototoxic, with photoindexes up to 17. Mechanistic studies indicated that such phototoxicity was due to a combination of photodynamic therapy (PDT) and photoactivated chemotherapy (PACT) effects, resulting from both reactive oxygen species generation and peptide photosubstitution. Finally, in vivo<\/i> studies in a subcutaneous U87MG glioblastoma mice model showed that [1<\/b>]Cl2<\/sub> efficiently accumulated in the tumor 12 h after injection, where green light irradiation generated a stronger tumoricidal effect than a nontargeted analogue ruthenium complex [2<\/b>]Cl2<\/sub>. Considering the absence of systemic toxicity for the treated mice, these results demonstrate the high potential of light-sensitive integrin-targeted ruthenium-based anticancer compounds for the treatment of brain cancer in vivo<\/i>.<\/p>\n","protected":false},"excerpt":{"rendered":"DOI: 10.1021\/jacs.3c04855 Authors: Liyan Zhang, Peiyuan Wang, Xue\u2010Quan Zhou, Ludovic Bretin, Xiaolong Zeng, Yurii Husiev, Ehider A. Polanco, Gangyin Zhao, Lukas S. Wijaya, Tarita Biver, Sylvia E. Le D\u00e9v\u00e9dec, Wen Sun, Sylvestre Bonnet Abstract: To investigate the potential of tumor-targeting photoactivated chemotherapy, a chiral ruthenium-based anticancer warhead, \u039b\/\u0394-[Ru(Ph2phen)2(OH2)2]2+, was conjugated to the RGD-containing Ac-MRGDH-NH2 peptide […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[19],"tags":[],"class_list":["post-822","post","type-post","status-publish","format-standard","hentry","category-mos500"],"_links":{"self":[{"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/posts\/822","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=822"}],"version-history":[{"count":0,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=\/wp\/v2\/posts\/822\/revisions"}],"wp:attachment":[{"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=822"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=822"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/citations.tools.bio-logic.fr\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=822"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}