دورية أكاديمية
Macrocyclic Dual-Locked “Turn-On” Drug for Selective and Traceless Release in Cancer Cells
| العنوان: | Macrocyclic Dual-Locked “Turn-On” Drug for Selective and Traceless Release in Cancer Cells |
|---|---|
| المؤلفون: | Schauenburg, Dominik, Gao, Bingjie, Rochet, Léa NC, Schüler, Darijan, Coelho, Jaime AS, Ng, David YW, Chudasama, Vijay, Kuan, Seah Ling, Weil, Tanja |
| المصدر: | Angewandte Chemie International Edition , Article e202314143. (2024) (In press). |
| بيانات النشر: | Wiley |
| سنة النشر: | 2024 |
| المجموعة: | University College London: UCL Discovery |
| مصطلحات موضوعية: | drug delivery, dual-responsive chemotherapeutics, macrocyclic drug, traceless release |
| الوصف: | Drug safety and efficacy due to premature release into the bloodstream and poor biodistribution remains a problem despite seminal advances in this area. To circumvent these limitations, we report drug cyclization based on dynamic covalent linkages to devise a dual lock for the small molecule anticancer drug, camptothecin (CPT). Drug activity is "locked" within the cyclic structure by the redox responsive disulfide and pH-responsive boronic acid-salicylhydroxamate and turns on only in the presence of acidic pH, reactive oxygen species and glutathione through traceless release. Notably, the dual-responsive CPT is more active (100-fold) than the non-cleavable (permanently closed) analogue. We further include a bioorthogonal handle in the backbone for functionalization to generate cyclic-locked, cell-targeting peptide- and protein-CPTs, for targeted delivery of the drug and traceless release in triple negative metastatic breast cancer cells to inhibit cell growth at low nanomolar concentrations. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| العلاقة: | https://discovery.ucl.ac.uk/id/eprint/10185375/1/Angew%20Chem%20Int%20Ed%20-%202024%20-%20Schauenburg%20-%20Macrocyclic%20Dual%E2%80%90Locked%20%20Turn%E2%80%90On%20%20Drug%20for%20Selective%20and%20Traceless%20Release%20in.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10185375Test/ |
| الإتاحة: | https://discovery.ucl.ac.uk/id/eprint/10185375/1/Angew%20Chem%20Int%20Ed%20-%202024%20-%20Schauenburg%20-%20Macrocyclic%20Dual%E2%80%90Locked%20%20Turn%E2%80%90On%20%20Drug%20for%20Selective%20and%20Traceless%20Release%20in.pdfTest https://discovery.ucl.ac.uk/id/eprint/10185375Test/ |
| حقوق: | open |
| رقم الانضمام: | edsbas.AF4203EC |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |