Design rules for externally triggered drug uncaging under optical and radiolytic regimes
Abstract
Externally triggered prodrug activation can improve therapeutic index by decoupling systemic distribution from pharmacological activity. This review examines prodrug uncaging strategies enabled by electromagnetic radiation through the lens of activation physics and clinical constraints, spanning UV-visible-near-infrared photochemistry and ionizing radiation. Differences in clinical applicability arise from fundamentally contrasting activation physics and irradiation geometry. While recent reviews have cataloged externally triggered prodrug systems across multiple modalities, we instead organize the field by activation regime and evaluate these systems under clinically realistic constraints. In photochemical activation, direct light-chromophore coupling enables predictable bond cleavage through defined excited-state pathways, but effective application is constrained by tissue optics and beam-sample geometry. X- and γ-rays penetrate deeply into tissues, but their uncaging pathway is indirect via diffusible water radiolysis products, resulting in stochastic rather than deterministic cleavage chemistry. We evaluate these platforms using deliverability, irradiation geometry, dose efficiency under clinically realistic conditions, microenvironment dependence, and functional group compatibility. We conclude with practical design rules and a decision framework that aligns targeted pathology and treatment objectives with the appropriate trigger chemistry, payload selection, and…
Read the paper
Related studies
- Developing high safety Li-metal anodes for future high-energy Li-metal batteries: strategies and perspectives
- Structure and Energy Transfer in Photosystems of Oxygenic Photosynthesis
- Ground- and Space-Based Gamma-Ray Astronomy
- Energy Functions in De Novo Protein Design: Current Challenges and Future Prospects
- Electronic structure of ions and molecules in solution: a view from modern soft X-ray spectroscopies
- Arising 2D Perovskites for Ionizing Radiation Detection
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.