NANOPARTICULATE PRODRUG DELIVERY SYSTEMS IN TARGETED CANCER THERAPY: FORMULATION APPROACHES, ACTIVATION MECHANISMS, AND TRANSLATIONAL PROSPECTS

Mrs. T. Arokkiya Ange*, Mr. A. N. Venkatesh, Ms. P. Priya

Conventional chemotherapeutic regimens continue to be hampered by inadequate tumor selectivity, systemic adverse effects, and the emergence of drug resistance. Over recent years, prodrug-incorporated nanoparticles (PNPs) have emerged as a powerful nanotechnology-driven platform to tackle these obstacles by merging rational prodrug design with sophisticated nanoscale delivery architectures. This review presents a thorough examination of the fundamental principles, structural classifications, and therapeutic prospects of prodrug-incorporated nanoparticles in targeted cancer treatment. By chemically converting active pharmaceutical ingredients into inactive or attenuated prodrug forms and incorporating them into nanoparticulate carriers, these platforms facilitate enhanced aqueous solubility, prolonged systemic circulation, programmed drug activation, and precise tumor localization. Particular focus is given to stimuli-activated PNPs that harness tumor-specific biological cues such as acidic microenvironmental pH, redox imbalances, enzyme upregulation, hypoxic states, and exogenous physical triggers to accomplish site-directed therapeutic release. The review elaborates on a variety of nanostructured architectures, encompassing polymer-drug conjugates, carrier-free self-assembling prodrug nanoassemblies, encapsulated prodrug formulations, and multidrug combination platforms. Preclinical and emerging clinical applications across principal cancer types—including breast, lung, brain, pancreatic, colorectal, ovarian cancers, and leukemia—are critically evaluated. Key barriers pertaining to large-scale fabrication, biosafety, regulatory compliance, and forward-looking directions involving artificial intelligence and individualized nanomedicine are also addressed. Collectively, prodrug-incorporated nanoparticles represent a versatile and scientifically robust nanotherapeutic strategy for realizing safer, more efficacious, and precision-guided oncological interventions.