Projects per year
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 the 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.
Original language | English |
---|---|
Pages (from-to) | 1747-1756 |
Journal | JACS Au |
Volume | 2 |
Issue number | 7 |
DOIs | |
Publication status | Published - 1 Jul 2022 |
Keywords / Materials (for Non-textual outputs)
- Bioorthogonal
- IEDDDA
- Cycloaddition
- Tumor Targeting
- Tumor Labeling
- Targeted Chemotherapy
Fingerprint
Dive into the research topics of 'Targeted Molecular Construct for Bioorthogonal Theranostics of PD- L1-Expressing Cancer Cells'. Together they form a unique fingerprint.Projects
- 1 Finished
-
Locally-Controlled Activation of Chemotherapeutics by Palladium Catalysis as a Novel Anticancer Technology
Unciti-Broceta, A. & Brennan, P.
1/04/16 → 30/09/21
Project: Research
Equipment
-
Edinburgh Drug Discovery
Asier Unciti-Broceta (Manager), Scott Webster (Manager) & Neil Carragher (Manager)
Deanery of Molecular, Genetic and Population Health SciencesFacility/equipment: Facility