Visualizing intracellular particles and precise control of drug release using an emissive hydrazone photochrome

The spatiotemporal control over the structure of nanoparticles while monitoring their localization in tumor cells can improve the precision of controlled drug release, thus enhancing the efficiency of drug delivery. Here, we report on a photochromic nanoparticle system (LSNP), assembled from fluorescent bistable hydrazone photoswitch-modified amphiphilic copolymers. The intrinsic emission of the hydrazone switch allows for the visualization of particle uptake, as well as their intracellular distribution. The Z → E photoswitching of the hydrazone switch within the nanoparticle leads to the expansion of the nanoparticles (i.e., drug release) accompanied by emission quenching, the degree of which can function as an internal indicator for the amount of drug released. The bistability of the switch enables the kinetic trapping of particles of different sizes as a function of irradiation time, and allows for the exhibition of light-dependent cell cytotoxicity in MDA-MB-231 cells using LSNP loaded with doxorubicin.