Targeted molecular construct for bioorthogonal theranostics of PD-L1-expressing cancer cells
Chow, Shiao Y. and Unciti-Broceta, Asier (2022) Targeted molecular construct for bioorthogonal theranostics of PD-L1-expressing cancer cells. JACS Au, 2 (7). 1747–1756. ISSN 2691-3704 (https://doi.org/10.1021/jacsau.2c00328)
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Abstract
Molecular targeting of tumor-overexpressed oncoproteins can improve the selectivity and tolerability of anticancer therapies. The immunoinhibitory membrane protein programmed death ligand 1 (PD-L1) is highly expressed on certain tumor types, which masks malignant cells from T cell recognition and creates an optimal environment for the cancer to thrive and spread. We report here a ligand-tetrazine conjugate (LTzC) armed with a PD-L1 small molecule inhibitor to selectively target PD-L1-expressing cancer cells and inhibit PD-L1 function and conjugated to a tetrazine module and a lipoyl group to incorporate bioorthogonal reactivities and an oxidative stress enhancer into the construct. By pairing LTzC with an imaging probe, we have established a “track-&-tag” system for selective labeling of PD-L1 both on and in living cells using click chemistry. We have further shown the specificity and versatility of LTzC by click-to-release activation of prodrugs and selective killing of PD-L1-expressing breast cancer cells, offering a new multimodal approach to “track-&-treat” malignant cells that are capable of evading the immune system.
ORCID iDs
Chow, Shiao Y. ORCID: https://orcid.org/0000-0002-3600-0497 and Unciti-Broceta, Asier;-
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Item type: Article ID code: 90383 Dates: DateEvent1 July 2022Published16 June 2022AcceptedSubjects: Medicine > Internal medicine > Neoplasms. Tumors. Oncology (including Cancer)
Science > Natural history > Biology
Science > Chemistry > Organic chemistryDepartment: Faculty of Science > Pure and Applied Chemistry Depositing user: Pure Administrator Date deposited: 27 Aug 2024 14:38 Last modified: 26 Oct 2024 00:42 URI: https://strathprints.strath.ac.uk/id/eprint/90383