Bright insights into palladium-triggered local chemotherapy

Bray, Thomas L.; Salji, Mark J.; Brombin, Alessandro; Pérez‐López, Ana M.; Rubio‐Ruíz, Belén; Galbraith, Laura C.A.; Patton, E. Elizabeth; Leung, Hing Y.; Unciti‐Broceta, Asier

doi:10.1039/c8sc02291g

Cited by 84 publications

(104 citation statements)

References 46 publications

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“…Indeed, several groups showed that organometallic activators can be used in the form of nano‐formulations that can be implanted during surgery or has the ability to accumulate at the tumor site based on the enhanced permeability and retention effect. After prodrug administration, these organometallic devices serve to produce the active drugs locally, which can have beneficial therapeutic effect . For intracellular applications, the metal catalyst can be fused to e. g. cell‐penetrating peptides …”

Section: Figurementioning

confidence: 99%

Transition‐Metal‐Mediated versus Tetrazine‐Triggered Bioorthogonal Release Reactions: Direct Comparison and Combinations Thereof

et al. 2020

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Bioorthogonal cleavage reactions are gaining popularity in chemically inducible prodrug activation and in the control of biomolecular functions. Despite similar applications, these reactions were developed and optimized on different substrates and under different experimental conditions. Reported herein is a side‐by‐side comparison of palladium‐, ruthenium‐ and tetrazine‐triggered release reactions, which aims at comparing the reaction kinetics, efficiency and overall advantages and limitations of the methods. In addition, we disclose the possibility of mutual combination of the cleavage reactions. Finally, we compare the efficiency of the bioorthogonal deprotections in cellular experiments, which revealed that among the three methods investigated, the palladium‐ and the tetrazine‐promoted reaction can be used for efficient prodrug activation, but only the tetrazine‐triggered reactions proceed efficiently inside cells.

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Section: Figurementioning

confidence: 99%

Transition‐Metal‐Mediated versus Tetrazine‐Triggered Bioorthogonal Release Reactions: Direct Comparison and Combinations Thereof

et al. 2020

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“…[53] Bray et al demonstrated that Pd 0 microdevices have the capacity to carry out ex vivo carbamate cleavage of masked doxorubicin in tumor tissues.T he Pd catalysts showedp romising biocompatibility when implanted in mice bearing prostate tumors and studies on zebrafish revealed that caged doxorubicin avoided the cardiotoxicity typicallyp roduced by the drug alone. [54] Ap ropargyl-masked prodrug of the histone deacetylase inhibitor vorinostat was also activated through Pd 0 catalysis. [55] The deprotection proceeded at physiological pH through at andem mechanism triggered by the Pd-catalyzed depropargylation.…”

Section: Transition-metal-mediated Bioorthogonal Catalysismentioning

confidence: 99%

Catalysis Concepts in Medicinal Inorganic Chemistry

Castro

Terenzi

Gurruchaga-Pereda

et al. 2019

Chemistry A European J

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Catalysis hass trongly emerged in the field of medicinal inorganic chemistry as as uitablet ool to deliver new drug candidates andt oo vercome drawbacks associated to metallodrugs.I nt his Concepta rticle, we discuss representative examples of how catalysis has been applied in combination with metal complexes to deliver new therapy approaches. In particular,w ee xplain key achievements in the design of catalytic metallodrugst hat damage biomolecular targets and in the development of metal catalysis schemes for the activation of exogenous organic prodrugs. Moreover,w ed iscusso ur recent discoveries on the flavin-mediated bioorthogonal catalytic activation of metal-basedp rodrugs;anew catalysis strategy in whichm etal complexes are unconventionallye mployed as substrates rather than catalysts.The ORCID identification number(s) for the author(s) of this articlecan be found under https://doi.

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“…Cells were independently treated with Pd‐microdevices (1 mg mL −1 ) or 2 c (−ve controls) or in combination (activation assay) and compared to treatment with unmodified 1 (+ve control) across a range of concentrations. As expected, the devices (which are larger than cells and remain in the extracellular space) displayed no toxic effect. In contrast, the Pd‐devices/ 2 c combination led to potent antiproliferative effect in all cell lines, slightly lower than that mediated by direct treatment with 1 .…”

Section: Resultsmentioning

confidence: 76%

“…Palladium (Pd) catalysts are one of the tools of choice currently under investigation to release caged drugs in vitro and in vivo . The selection of this metal is based on its high bio‐compatibility, its versatility to adopt different shapes and sizes and its remarkable capabilities to catalyze N ‐ and O ‐dealkylation reactions on manifold types of substrates under physiological conditions .…”

Section: Introductionmentioning

confidence: 99%

Bioorthogonal Uncaging of the Active Metabolite of Irinotecan by Palladium‐Functionalized Microdevices

Adam

Pérez‐López

Hamilton

et al. 2018

Chemistry A European J

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SN‐38, the active metabolite of irinotecan, is released upon liver hydrolysis to mediate potent antitumor activity. Systemic exposure to SN‐38, however, also leads to serious side effects. To reduce systemic toxicity by controlling where and when SN‐38 is generated, a new prodrug was specifically designed to be metabolically stable and undergo rapid palladium‐mediated activation. Blocking the phenolic OH of SN‐38 with a 2,6‐bis(propargyloxy)benzyl group led to significant reduction of cytotoxic activity (up to 44‐fold). Anticancer properties were swiftly restored in the presence of heterogeneous palladium (Pd) catalysts to kill colorectal cancer and glioma cells, proving the efficacy of this novel masking strategy for aromatic hydroxyls. Combination with a Pd‐activated 5FU prodrug augmented the antiproliferative potency of the treatment, while displaying no activity in the absence of the Pd source, which illustrates the benefit of achieving controlled release of multiple approved therapeutics—sequentially or simultaneously—by the same bioorthogonal catalyst to increase anticancer activity.

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Bright insights into palladium-triggered local chemotherapy

Abstract: We report fundamental insights into the validity, reliability and clinical feasibility of using heterogeneous Pd catalysts as implantable devices to accurately activate chemotherapy within a tumour.

Cited by 84 publications

References 46 publications

Transition‐Metal‐Mediated versus Tetrazine‐Triggered Bioorthogonal Release Reactions: Direct Comparison and Combinations Thereof

Transition‐Metal‐Mediated versus Tetrazine‐Triggered Bioorthogonal Release Reactions: Direct Comparison and Combinations Thereof

Catalysis Concepts in Medicinal Inorganic Chemistry

Bioorthogonal Uncaging of the Active Metabolite of Irinotecan by Palladium‐Functionalized Microdevices

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