Building bioorthogonal click-release capable artificial receptors on cancer cell surface for imaging, drug targeting and delivery.
10.1016/j.apsb.2022.12.018
- Author:
Jing CHEN
1
;
Peng JI
1
;
Giri GNAWALI
1
;
Mengyang CHANG
2
;
Feng GAO
1
;
Hang XU
1
;
Wei WANG
1
Author Information
1. Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ 85721, USA.
2. Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA.
- Publication Type:Journal Article
- Keywords:
Artificial receptor;
Click and release;
Local activation;
Protein degradation
- From:
Acta Pharmaceutica Sinica B
2023;13(6):2736-2746
- CountryChina
- Language:English
-
Abstract:
The current targeting drug delivery mainly relies on cancer cell surface receptors. However, in many cases, binding affinities between protein receptors and homing ligands is relatively low and the expression level between cancer and normal cells is not significant. Distinct from conventional targeting strategies, we have developed a general cancer targeting platform by building artificial receptor on cancer cell surface via a chemical remodeling of cell surface glycans. A new tetrazine (Tz) functionalized chemical receptor has been designed and efficiently installed on cancer cell surface as "overexpressed" biomarker through a metabolic glycan engineering. Different from the reported bioconjugation for drug targeting, the tetrazine labeled cancer cells not only locally activate TCO-caged prodrugs but also release active drugs via the unique bioorthogonal Tz-TCO click-release reaction. The studies have demonstrated that the new drug targeting strategy enables local activation of prodrug, which ultimately leads to effective and safe cancer therapy.
