Naphthalene-Derived Photo-Switchable Hyperbranched Polymer by Anionic Polymerization for the Early Stage Detection and Monitoring Azoreductase Activity under Hypoxic Environment

The design and synthesis of macromolecules through controlled branching via hyperbranch polymerization have recently attracted attention from the scientific community due to their diverse biomedical applications, including diagnosis and drug delivery. This article highlights the development of a naphthalene-derived, photoswitchable, self-assembling hyperbranch polymer (<b>PNap-Azo</b>) in an aqueous medium, in which the azo bond serves as a stimulus-responsive feature in the presence of an overexpressed enzyme in a hypoxic microenvironment. <b>PNap-Azo</b> has a significant biological impact in hypoxic environments due to an azo bond (N═N), which transforms from a spherical to a twisted-rod shape upon cis-trans isomerization. Due to its amphiphilic nature and extensive hydrogen bonding, it exhibits an excellent twisted-rod morphology, enhancing the polymer's therapeutic efficacy in a hypoxic tumor environment. Therefore, <b>PNap-Azo</b> can detect and monitor azoreductase activity in a hypoxic environment through turn-on fluorescence responses, which are verified both spectroscopically and biologically in live cell lines. Our synthesized polymer, <b>PNap-Azo</b>, can monitor azoreductase activity in real time, potentially preventing complications before the condition worsens.