Abstract: 
Conventional chemotherapy has drug resistance and systemic toxicity and low tumor selectivity. Drug resistance, systemic toxicity, and low tumor selectivity are the problems that remain with conventional chemotherapy. In the past few years, a novel technique that integrates logical prodrug design and the development of sophisticated nanoscale delivery systems has been developed, namely the prodrug-based nanoparticles (PNPs). This review is a comprehensive summary of the principles, classification and therapeutic applications of nanoparticles in precision oncology via prodrug approach. These systems can be used to make active drugs inactive or less active as prodrugs, and can be engineered to circulate in blood for longer after administration, to be activated at the tumour site and to target the tumour. Particular attention is given to PNPs sensitive to external stimuli or to tumor specific stimuli like acidic pH, redox imbalance, overexpression of enzymes, hypoxic condition, etc., which enable the drug release in the tumor site. The review also covers various kinds of nanoarchitecture: polymer–drug conjugates, self-assembling prodrug nanoassemblies based on small molecules, encapsulated prodrug systems, as well as combination therapy platforms. Cancers like breast cancer, lung cancer, brain cancers, pancreatic cancers, colorectal cancers, leukemia, and ovarian cancers are also given attention with regard to preclinical and developing clinical studies as examples. Finally, there are some aspects about mass production, safety, translational and future perspectives of artificial intelligence and personalized nanomedicine that need to be mentioned. In summary, the development of nanoparticle-based prodrugs is an exciting and multifunctional nanotechnology solution to cancer treatment.

Keywords: Prodrug-Based Nanoparticles, Nanotechnology, Precision Oncology, Stimuli-Responsive Drug Delivery, Cancer Nanomedicine, Targeted Therapy, Prodrug Nanocarrier.