Bright insights into palladium-triggered local chemotherapy

Bray, T. L., Salji, M. , Brombin, A., Pérez-López, A. M., Rubio-Ruiz, B., Galbraith, L. C.A., Patton, E. E., Leung, H. Y. and Unciti-Broceta, A. (2018) Bright insights into palladium-triggered local chemotherapy. Chemical Science, 9(37), pp. 7354-7361. (doi: 10.1039/c8sc02291g)

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Abstract

The incorporation of transition metal catalysts to the bioorthogonal toolbox has opened the possibility of producing supra-stoichiometric amounts of xenobiotics in living systems in a non-enzymatic fashion. For medical use, such metals could be embedded in implantable devices (i.e. heterogeneous catalyst) to “synthesize” drugs in desired locations (e.g. in a tumour) with high specificity and for extended periods of time, overcoming the useful life limitations of current local therapy modalities directed to specific organ sites (e.g. brachytherapy, controlled release systems). To translate this approach into a bona fide therapeutic option, it is essential to develop clinically-accessible implantation procedures and to understand and validate the activation process in relevant preclinical models. Herein we report the development of a novel Pd-activatable precursor of the red-fluorescent drug doxorubicin and Pd devices of optimized size and activity. Screening in state-of-the-art cancer models provided fundamental insights into the insertion protocols, safety and stability of the devices and into the prodrug distribution profile before and after activation.

Item Type:Articles
Additional Information:We thank EPSRC (Healthcare Technology Challenge Award EP/ N021134/1) and CRUK (CRT Project Development Fund) for funding the project. T. L. B. thanks the CMVM of the University of Edinburgh (Principal's scholarship). M. S. and H. Y. L. are grateful to MRC (Clinical Research Fellowship 70128) and CRUK (Beatson Institute A15151), respectively. A. T. and E. E. P. thanks MRC (MC_PC_U127585840), ERC (ZF-MEL-CHEMBIO648489) and the Melanoma Research Alliance – L'Oreal USA (401181). B. R.-R. thanks the EC (H2020-MSCA-IF-2014-658833, ChemoBOOM).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Leung, Professor Hing and Salji, Dr Mark and Galbraith, Dr Laura
Authors: Bray, T. L., Salji, M., Brombin, A., Pérez-López, A. M., Rubio-Ruiz, B., Galbraith, L. C.A., Patton, E. E., Leung, H. Y., and Unciti-Broceta, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Chemical Science
Publisher:Royal Society of Chemistry
ISSN:2041-6520
ISSN (Online):2041-6539
Published Online:17 July 2018
Copyright Holders:Copyright © 2018 The Royal Society of Chemistry
First Published:First published in Chemical Science 9(37): 7354-7361
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
706251Palladium-activated prodrug therapy: a novel focal therapy for localised cancers of unmet needHing LeungEngineering and Physical Sciences Research Council (EPSRC)EP/N021134/1ICS - CLINICAL TRIALS RESEARCH