Taha, Bakr AhmedBakr AhmedTahaAddie, Ali J.Ali J.AddieAl-Rawi, Marwa AminMarwa AminAl-RawiHaider, Adawiya J.Adawiya J.HaiderYadav, Amit K.Amit K.YadavBhatia, DhirajDhirajBhatiaJabir, Majid S.Majid S.JabirIbnaouf, Khalid HassanKhalid HassanIbnaoufArsad, NorhanaNorhanaArsad2025-11-262025-11-262025-12-0110.1016/j.jddst.2025.1074882-s2.0-105021082102http://repository.iitgn.ac.in/handle/IITG2025/33520Drug resistance is a major worldwide health issue, with a growing incidence leading to increased morbidity and mortality. Molecular diagnostics require solutions that combine sensitivity, flexibility, and responsiveness. This review summarizes current understanding of the involvement of enzymes in the many processes that drive drug resistance and discusses the possible uses of enzyme-responsive nanomaterials. It investigates modern strategies used in the literature to monitor and mitigate drug resistance processes, such as Surface-Enhanced Raman Scattering (SERS), fluorescence imaging, CRISPR-based diagnostics, and near-infrared (NIR) detection. Published research shows that combining enzyme-responsive nanomaterials with photonic technology is a potential technique for detection of drug resistance and molecular sensing. These nanoplatforms allow for the quick and selective detection of disease biomarkers, such as enzymes associated with diseased states and resistant phenotypes, using enzyme-triggered activation mechanisms and photonic signal transduction. As a result, localized therapeutic release is demonstrated to enhance therapy specificity and reduce systemic toxicity. Moreover, insights into the molecular processes that underpin drug resistance improve our understanding of drug modification and metabolism. Advances in nanotechnology, artificial intelligence, and machine learning are increasing our ability to analyze enzyme behavior and inform treatment plans. By incorporating diagnostic and therapeutic capabilities into adaptable nanoplatforms, the reviewed approaches represent a significant step forward in smart nanomedicine. Consequently, it provides new possibilities for the treatment of drug-resistant cancers and infectious diseases in an environmentally friendly approach.falseDrug resistance | Enzyme responsive | Nanomaterials | Nanophotonics biosensorSmart nanophotonics for enzyme-driven drug resistance sensing and controlled therapeutic releaseArticleDecember 20250107488WOS:001567356900006