Radiopaque poly(5-acrylamido-2,4,6-triiodoisophthalic acid)-based copolymers as theranostic carriers for image-guided drug delivery

Advancements in disease understanding have led to a shift towards personalized medicine, which has driven the development of an approach called theranostics. This approach combines diagnostics and therapy in one integrated system. Radiopaque biomaterials allow for non-invasive imaging using X-ray and computed tomography (CT). However, conventional contrast agents like gold nanoparticles are costly and are not well-suited for drug encapsulation. In this study, new block and statistical copolymers were synthesized using reversible addition-fragmentation chain-transfer (RAFT) polymerization comprising poly(<i>N</i>-isopropylacrylamide) (PNIPAM) and poly(5-acrylamido-2,4,6-triiodoisophthalic acid) (PAATIPA), designed to combine radiopacity with drug delivery capabilities. PAATIPA's high iodine content provides strong contrast in CT scans, while PNIPAM's thermoresponsiveness allows for self-assembly at higher temperatures. The anionic nature of PAATIPA allows the efficient encapsulation of the cationic small-molecule rhodamine 6G. The copolymers exhibited an enhanced encapsulation of cationic rhodamine 6G (>90% at 35 w/w% of rhodamine) and excellent biocompatibility, as demonstrated in cytotoxicity assays. This study emphasizes the potential of PAATIPA-based copolymer materials as multifunctional, radio-opaque and stimuli-responsive materials for theranostic applications.