Selenium-Containing Polymers: In Vivo Modulation and Radioprotection

Conspectus Selenium is an essential element widely utilized across biological systems, where it imparts unique chemical functionality to biomacromolecules. While selenoproteins are well appreciated in humans, other selenium-containing biomacromolecules remain largely absent, and the development of selenium-based therapeutics has lagged. Here, from the perspective of molecular design, we introduce a series of selenium-containing polymers with diverse molecular structures and elucidate their in vivo effect, aiming to advance selenium chemistry toward defined biological functions. In this account, we establish a unified framework linking molecular structure, chemical reactivity, and in vivo functionality of selenium-containing polymers, thereby redefining their role beyond conventional drug carriers. We first delineate the distinct redox-responsive behaviors of monoselenide and diselenide motifs and their divergent biological consequences in vivo. We then introduce selenium-doped carbonized polymer dots for the treatment of liver and kidney diseases. Finally, we discuss selenium-containing melanins as a previously unrecognized class of selenium-enriched biomacromolecules with exceptional radioprotective capability, arising from their conjugated structures and selenium-specific electronic properties. By integrating these structurally related yet functionally diverse systems, this account highlights general design principles for in vivo modulation using selenium polymer chemistry. Bridging the gap between biological selenium utilization and synthetic molecular design unlocks new opportunities for selenium-based therapeutics and establishes selenium-containing polymers as a distinctive platform in biomedical science.