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

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.

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.

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.

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.

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.