Electrochemical activation of chemotherapeutic prodrugs that mimic P450-catalyzed oxidation: proof-of-concept for a focal approach to chemical cancer treatment
Bibliographic record
Abstract
The electrochemical oxidation of substrates cyclophosphamide and acetaminophen at Ti/RuO2 or (preferably) graphite anodes parallels P450-catalyzed oxidation in that both mechanisms involve transfer of an oxygen atom to the substrate. The aim of this work was to use this parallel to provide proof-of-concept for a localized approach to tumor chemotherapy using electrochemical oxidation to activate chemotherapeutic prodrugs ex situ. Cyclophosphamide and acetaminophen were electroactivated in batch and flow electrolytic cells and the products were tested against EMT6 mouse mammary adenocarcinoma cells. Cell viability was determined using a tetrazolium dye assay that monitored NADPH concentrations; microscopic examination showed consistent morphological differences between viable and nonviable cells. No cytotoxicity was observed in nonelectrolyzed control samples. The electrolyzed prodrugs demonstrated cytotoxicity up to the IC99 level at 5 mmol L−1 initial prodrug concentrations but not at 1 mmol L−1. The long-term objective of the work is to develop an ex situ electrochemical system for activating prodrugs to cause lethal toxicity to the cells of solid tumors, many of which lack sufficient P450s to bioactivate the toxicant themselves.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".