Electrodrugs: an electrochemical prodrug activation strategy

Norman, Daniel J.; González‐Fernández, Eva; Clavadetscher, Jessica; Tucker, Lulu H; Staderini, Matteo; Mount, Andrew R.; Murray, Alan F.; Bradley, Mark

doi:10.1039/c8cc04151b

Cited by 16 publications

(9 citation statements)

References 20 publications

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“…Furthermore, the electric field is another emerging method to trigger the release of prodrugs. For example, J. Norman et al presented a new concept of electroceuticals, summarized as the electrochemical activation of metal-based prodrugs [69]. However, due to the limitations of the electric field applied in vivo, there is little research on this part.…”

Section: Magnetism and Electric Field -Responsivementioning

confidence: 99%

Stimuli-responsive prodrug-based cancer nanomedicine

et al. 2020

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The rapid development of nanotechnology results in the emergence of nanomedicines, but the effective delivery of drugs to tumor sites remains a great challenge. Prodrug-based cancer nanomedicines thus emerged due to their unique advantages, including high drug load efficiency, reduced side effects, efficient targeting, and real-time controllability. A distinctive characteristic of prodrug-based nanomedicines is that they need to be activated by a stimulus or multi-stimulus to produce an anti-tumor effect. A better understanding of various responsive approaches could allow researchers to perceive the mechanism of prodrugbased nanomedicines effectively and further optimize their design strategy. In this review, we highlight the stimuli-responsive pathway of prodrug-based nanomedicines and their anticancer applications. Furthermore, various types of prodrug-based nanomedicines, recent progress and prospects of stimuli-responsive prodrug-based nanomedicines and patient data in the clinical application are also summarized. Additionally, the current development and future challenges of prodrug-based nanomedicines are discussed. We expect that this review will be valuable for readers to gain a deeper understanding of the structure and development of prodrug-based cancer nanomedicines to design rational and effective drugs for clinical use.

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Section: Magnetism and Electric Field -Responsivementioning

confidence: 99%

Stimuli-responsive prodrug-based cancer nanomedicine

et al. 2020

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“… 7 Polyethylene glycol (PEG) “protected or blocked” interleukin-2 (IL-2) is a biologic prodrug with IL-2 liberated by in vivo release of the PEG chains. 8 Other, more academic prodrug stimuli have been explored in a variety of models, including electrochemical activation of metal-based prodrugs, 9 ultrasound-induced release, 10 or light mediated activation. 11 …”

Section: Introductionmentioning

confidence: 99%

Switching on prodrugs using radiotherapy

et al. 2021

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Chemotherapy is a powerful tool in the armoury against cancer, however it is fraught with problems due to global systemic toxicity. Here we report the proof-of-concept of a chemistry-based strategy, whereby gamma/X-ray irradiation mediates the activation of a cancer prodrug thereby enabling simultaneous chemoradiotherapy with radiotherapy locally activating a prodrug. In an initial demonstration we show the activation of a fluorescent probe using this approach. Expanding on this, we show how sulfonyl azide and phenyl azide caged prodrugs of pazopanib and doxorubicin, can be liberated using clinically relevant doses of ionising radiation. This strategy is different to conventional chemo-radiotherapy radiation, where chemo-sensitization of the cancer takes place so that subsequent radiotherapy is more effective. This approach could enable site directed chemotherapy, rather than systemic chemotherapy, with “real time” drug decaging at the tumour site. As such it opens up a new era in targeted and directed chemotherapy.

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“…Bio-orthogonal approaches aim to overcome limitations of biological specificity by modulating drug activity in a manner that is independent of naturally occurring chemical processes. Previously studied strategies for triggered activation of cancer prodrugs have used electrochemical, ultrasonic, optical, , copper-free click chemical, , and transition-metal catalytic , activation schemes. It has generally been a challenge to achieve highly localized control of drug activation deep through tissue in a noninvasive manner.…”

Section: Introductionmentioning

confidence: 99%

Radiation Cleaved Drug-Conjugate Linkers Enable Local Payload Release

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Arboleda-Prado

et al. 2022

Bioconjugate Chem.

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Conjugation of therapeutic payloads to biologics including antibodies and albumin can enhance the selectively of drug delivery to solid tumors. However, achieving activity in tumors while avoiding healthy tissues remains a challenge, and payload activity in off-target tissues can cause toxicity for many such drug-conjugates. Here, we address this issue by presenting a drug–conjugate linker strategy that releases an active therapeutic payload upon exposure to ionizing radiation. Localized X-ray irradiation at clinically relevant doses (8 Gy) yields 50% drug (doxorubicin or monomethyl auristatin E, MMAE) release under hypoxic conditions that are traditionally associated with radiotherapy resistance. As proof-of-principle, we apply the approach to antibody– and albumin–drug conjugates and achieve >2000-fold enhanced MMAE cytotoxicity upon irradiation. Overall, this work establishes ionizing radiation as a strategy for spatially localized cancer drug delivery.

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Electrodrugs: an electrochemical prodrug activation strategy

Cited by 16 publications

References 20 publications

Stimuli-responsive prodrug-based cancer nanomedicine

Stimuli-responsive prodrug-based cancer nanomedicine

Switching on prodrugs using radiotherapy

Radiation Cleaved Drug-Conjugate Linkers Enable Local Payload Release

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