Acetaminophen-loaded nanomaterials for cancer therapy: Recent advances and future perspectives

The commonly used analgesic/antipyretic drug acetaminophen (APAP) is being investigated for experimental cancer therapy. The hepatotoxic intermediate N-acetyl-p-benzoquinone imine (NAPQI) is generated by cytochrome P450 metabolism in the liver. Some tumor-directed strategies have utilized the tyrosinase-mediated activation of APAP to generate cytotoxic quinone metabolites such as 4-acetamido-o-benzoquinone (AOBQ). Nanocarrier-based delivery methods provide a means to address these constraints by increasing drug localization, controlling release behavior and by interaction with specific tumor microenvironmental properties. This review covers current achievements in the development of APAP-loaded materials for cancer-related applications, including formulation methodologies, drug–carrier interactions, physicochemical properties, release mechanisms and biological consequences. The many delivery platforms, including polymeric, lipid-based, inorganic and hybrid systems are examined in terms of their potential to increase APAP delivery and therapeutic performance. Furthermore, the importance of stimuli-responsive systems for better tumor-selective activation and to overcome the current limits of APAP-based techniques is assessed. Finally, the challenges in biological validation, safety assessment and clinical translation of APAP loaded nanomaterials are discussed. Overall, the available evidence supports the use of APAP-based nanomedicine as an early-stage experimental approach rather than an established cancer treatment. Further studies are required to show tumor-selective efficacy, pharmacokinetic benefits and long term safety before its clinical potential can be established.