The Road to Precision Nanomedicine: An Insight on Drug Repurposing and Advances in Nanoformulations for Treatment of Cancer.

Cancer remains one of the most significant global health challenges, with its burden continuing to rise. The limitations of conventional anticancer therapies caused by the lack of tissue selectivity, demands urgent development of safer and more selective therapies to target tumors. Identifying the fundamental cancer hallmarks provided a comprehensive understanding of cancer biology for effective tumor targeting, encompassing tumor-promoting inflammation, metabolic reprogramming, immune evasion, genomic instability, phenotypic plasticity, epigenetic reprogramming, and polymorphic microbiomes. Moreover, drug repurposing is a cost-effective and time-saving method for cancer therapy that accelerates the drug discovery process by reusing drugs for new indications. Current research is focusing on combining drug repurposing with nanocarriers that enhance tumor targeting, reduce the side effects, and improve the bioavailability of the drug in a single nanoformulation. This article analyzes various types of nanoparticles encapsulating different classes of drugs, such as phenelzine, fexofenadine, telmisartan, losartan, metformin, canagliflozin, atorvastatin, and fenbendazole, highlighting their anticancer effects and the influence of nanocarriers on the drug's therapeutic effect. Results revealed that drug-encapsulated nanoparticles enhanced antitumor effects compared to the free drug solutions. This is attributed to the synergism from the nanocarrier's functionalization, sustained drug release, and improved cellular uptake within tumors that leads to targeting multiple cancer hallmarks. Additionally, this review highlights the present challenges in the clinical translation of nanoformulation and demonstrates how artificial intelligence may facilitate drug screening and identification, therapeutic optimization, and large-scale manufacture. Finally, using these technologies in combination with drug repurposing presents a promising direction for advancing cancer treatment.