Targeting Metabolic Dysfunctions in Cancer through Nanoparticles: Advances in Therapeutic Delivery.

INTRODUCTION: Cancer progression is characterized by metabolic reprogramming, including the enhanced Warburg effect, hypoxia-driven adaptations, ferroptosis regulation, and altered lipid metabolism. These metabolic changes promote tumor growth, survival, metastasis, and therapeutic resistance. This review aims to analyze the recent advances in nanoparticle-based strategies designed to target metabolic vulnerabilities in cancer and ameliorate therapeutic outcomes. METHODS: A comprehensive analysis of recent studies was performed to examine nanoparticle-based interventions targeting key metabolic pathways in cancer. Different nanocarrier platforms, including polymeric, lipidbased, metallic, and biomimetic nanoparticle was assessed regarding their design, targeting mechanisms, and metabolic dysregulation capabilities. RESULTS: Various nanoparticle systems have demonstrated considerable potential for selectively disrupting tumor metabolism. Polymeric nanoparticles provide controlled drug release and structural flexibility for targeted delivery. Conversely, lipid-based nanocarriers offer high biocompatibility. At the same time, metallic nanoparticles exhibit strong oxidative stress induction. Several studies also reported enhanced therapeutic efficacy through codelivery approaches and stimulus-responsive drug release. DISCUSSION: Targeting cancer metabolism through nanotechnology offers significant advantages over conventional therapies by improving drug stability, bioavailability, and tumor specificity. Nevertheless, major challenges remain, including metabolic adaptability, off-target toxicity, variability in nanoparticle accumulation, and manufacturing complexities. Addressing these barriers requires a deeper understanding of metabolic interactions within the tumor microenvironment and the development of more precise, safe, and scalable nanoparticles. CONCLUSION: Nanoparticle-mediated targeting of cancer metabolism represents a promising therapeutic strategy. However, successful clinical translation requires improved understanding of metabolic networks, optimized nanoparticle design, and standardized evaluation frameworks.