Novel Bioorthogonal Theranostic Scaffold Enables on-Target Drug Release and Real Time Monitoring In Vivo DOI

Jing Pang,

Shun Feng,

Bin Huang

et al.

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

Bioorthogonal chemistry-based prodrug strategy features spatiotemporally controlled release of therapeutic agent and/or imaging probe. However, the integration diagnosis and therapy into a single molecule paired with bioorthogonal trigger remains challenge. In this study, we devised novel theranostic scaffold amenable to conjugation various targeting click-to-release reaction enable targeted drug liberation concomitant fluorescence emission. Such one-stone-three-birds consists new fluorophore phenanthrodioxine (PDO) linked masking group, tetrazine (Tz) which serves as dual switch for activation drug. Further installation warhead phenylboronic acid (PBA) ensures accumulation resultant PBA-PDO-Tz conjugate in tumor cells, thereby achieving on-demand trans-cyclooctene-caged anticancer Doxorubicin real-time monitoring on-target cytotoxicity live cells an A549 xenograft mouse model. The trigger-dual response holds promise precise theranostics applications vivo.

Language: Английский

Novel Bioorthogonal Theranostic Scaffold Enables on-Target Drug Release and Real Time Monitoring In Vivo DOI

Jing Pang,

Shun Feng,

Bin Huang

et al.

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

Bioorthogonal chemistry-based prodrug strategy features spatiotemporally controlled release of therapeutic agent and/or imaging probe. However, the integration diagnosis and therapy into a single molecule paired with bioorthogonal trigger remains challenge. In this study, we devised novel theranostic scaffold amenable to conjugation various targeting click-to-release reaction enable targeted drug liberation concomitant fluorescence emission. Such one-stone-three-birds consists new fluorophore phenanthrodioxine (PDO) linked masking group, tetrazine (Tz) which serves as dual switch for activation drug. Further installation warhead phenylboronic acid (PBA) ensures accumulation resultant PBA-PDO-Tz conjugate in tumor cells, thereby achieving on-demand trans-cyclooctene-caged anticancer Doxorubicin real-time monitoring on-target cytotoxicity live cells an A549 xenograft mouse model. The trigger-dual response holds promise precise theranostics applications vivo.

Language: Английский

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