The treatment of glioblastoma (GBM) represents an urgent challenge for public health due to the inability to effectively deliver anticancer agents, such as doxorubicin (DOX), through the blood-brain barrier (BBB). Herein we report the synthesis of two novel DOX glycoconjugates using an oxime linkage that maintained the intercalation capability of the planar anthracycline ring of DOX, as demonstrated by UV–vis and fluorescence experiments in the presence of DNA. The biological effect of DOX glycoconjugates was evaluated in GBM cell lines, showing an enhanced cytotoxic and pro-apoptotic effect of 7 as compared to 4 and to conventional DOX. These data were confirmed in an in vitro coculture BBB model in which DOX glycoconjugate 7 showed high capability to cross a cellular monolayer and exert its cytotoxic effect on GBM cells. The results show that conjugation with glucose may represent a helpful tool to increase chemotherapy effectiveness in poor-responding GBM patients.

Oxime Linked Doxorubicin Glycoconjugates Improve the Specific Targeting of Glioblastoma in High-Grade Glioma Therapy / Iorio, Anna Lisa; Lenci, Elena; Marzano, Chiara; Bucaletti, Elisabetta; Tirinnanzi, Bianca; Casati, Giacomo; Giunti, Laura; Dallari, Caterina; Credi, Caterina; Sardi, Iacopo; Trabocchi, Andrea. - In: ACS MEDICINAL CHEMISTRY LETTERS. - ISSN 1948-5875. - STAMPA. - 15:(2024), pp. 1953-1960. [10.1021/acsmedchemlett.4c00398]

Oxime Linked Doxorubicin Glycoconjugates Improve the Specific Targeting of Glioblastoma in High-Grade Glioma Therapy

Iorio, Anna Lisa;Lenci, Elena;Bucaletti, Elisabetta;Casati, Giacomo;Dallari, Caterina;Credi, Caterina;Sardi, Iacopo
;
Trabocchi, Andrea
2024

Abstract

The treatment of glioblastoma (GBM) represents an urgent challenge for public health due to the inability to effectively deliver anticancer agents, such as doxorubicin (DOX), through the blood-brain barrier (BBB). Herein we report the synthesis of two novel DOX glycoconjugates using an oxime linkage that maintained the intercalation capability of the planar anthracycline ring of DOX, as demonstrated by UV–vis and fluorescence experiments in the presence of DNA. The biological effect of DOX glycoconjugates was evaluated in GBM cell lines, showing an enhanced cytotoxic and pro-apoptotic effect of 7 as compared to 4 and to conventional DOX. These data were confirmed in an in vitro coculture BBB model in which DOX glycoconjugate 7 showed high capability to cross a cellular monolayer and exert its cytotoxic effect on GBM cells. The results show that conjugation with glucose may represent a helpful tool to increase chemotherapy effectiveness in poor-responding GBM patients.
2024
15
1953
1960
Goal 3: Good health and well-being
Iorio, Anna Lisa; Lenci, Elena; Marzano, Chiara; Bucaletti, Elisabetta; Tirinnanzi, Bianca; Casati, Giacomo; Giunti, Laura; Dallari, Caterina; Credi, ...espandi
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1399744
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