Photoinitiated Radical Thiol–Ene/Methacrylate versus Thia-Michael Addition in Polyurethane-Grafted Networks: A Comparative Study of Polymeric Drug Delivery Platforms

Abstract

In the age of advanced polymer science and regenerative medicine, biomaterial platforms are being developed that combine therapeutic functionality and molecular precision, providing fresh hope for the treatment of complex diseases, such as cancer. Translating these adaptable chemistries into biomedical practice necessitates a nuanced comprehension of how subtle variations in network formation mechanisms affect the practical outcomes. Herein, copolymers were synthesized using a base-catalyzed thia-Michael addition and a photoinitiated radical thiol–ene/methacrylate reaction, respectively, and subsequently grafted with polyurethane to yield corresponding grafted copolymers. A comprehensive comparison was carried out using 1H NMR and GPC for structural analysis, dynamic shear rheology for melt-state viscoelasticity, and alamarBlue alongside ROS and caspase-3 assays for evaluating anticancer efficacy against MDA-MB-231 cells. Results show that the base-initiated click reaction yielded a greater thiol conversion (47.5%) and a more homogeneous network compared to the photoinitiated approach (22.8%). While both graft copolymers exhibited significant shear thinning and thermoplastic behavior, the highly cross-linked photo-based polymer (Graft-P) showed a greater steady shear viscosity. Ultimately, the thia-Michael polyurethane-grafted network (Graft-C) with tailored hydrophilic–hydrophobic balance provided better sustained paclitaxel release, resulting in about 70% cancer cell mortality over 72 h as opposed to 55% for the photo-based grafted polymer network. Through this integrative approach, we demonstrate how tuning backbone chemistry and postsynthetic grafting drives functional performance and shape the next generation of engineered biomaterials: more resilient, tunable, and better predictive in their biological interactions, well-suited for advanced healthcare applications, especially cancer treatment.