Science of Synthesis

Porte, K.; Thoreau, F.; Papot, S.; Taran, F., Science of Synthesis: Abiotic Reactions in Live Environments, (2024) 1, 353.

General Introduction

The idea of a “magic bullet,” popularized by Paul Ehrlich in 1907, which defines a highly selective drug that acts only in diseased tissues while sparing healthy organs, has inspired generations of scientists to devise personalized therapies. To some extent, such a concept has become reality with the recent development of antibody–drug conjugates (ADCs),[‌1‌,‌2‌] as these were designed for the selective delivery of potent cytotoxic drugs within targeted cancer cells. However, in the case of ADCs approved to date, the process of drug release is triggered by endogenous stimuli [enzymes, pH, reactive oxygen species (ROS)], resulting in off-target activation of the cytotoxic agent, therefore provoking adverse effects associated with the destruction of healthy cells.[‌3‌] This example highlights that biotic reactions are not ideal candidates to modulate drug properties (e.g., active/inactive) with stringent spatiotemporal control, since the biochemical differences between normal and diseased tissues are usually limited. Therefore, the use of abiotic chemistry, which refers to chemical reactions that are not used by living systems, has been considered recently for designing more-selective therapeutic approaches.

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References