Light-responsive Self-Immolative L-glutamic Acid-based Polyester Nanoparticles for Controlled Drug Release via Passerini Three-Component Polymerization

L-glutamic acid (LA) is a bio-based, non-toxic, environmentally friendly material derived from biomass. The present study reports the application of Passerini three-component polymerization (P-3CP) for the straightforward preparation of LA-based light-responsive polyesters (PLTDs) under mild conditions. PLTDs with molar masses up to 8500 g/mol and high yields exceeding 90% are obtained. The chemical structures and light-responsive self-immolative behavior of PLTDs are comprehensively characterized by employing ultraviolet-visible (UV-Vis) spectroscopy, size exclusion chromatography (SEC), nuclear magnetic resonance (NMR) spectroscopy, and liquid chromatography mass spectrometry (LC-MS). Meanwhile, monodisperse PLTD-based doxorubicin-loaded nanoparticles (PLTD-DOX-NP) (size=193 nm, PDI=0.018) are formulated by nanoprecipitation method. Upon light-induced depolymerization, the PLTD-DOX-NP undergoes rapid decomposition, resulting in a burst release of 80% cargo within 13 s. Furthermore, according to biological toxicity tests, the PLTD-NP possesses adequate biosafety, both before and after irradiation. Overall, the incorporation of P-3CP with biorenewable LA-based monomer adheres to the principles of green chemistry, significantly simplifying the synthetic pathway of light-responsive polymers.