Nanoplatform-mediated metabolic reprogramming to overcome resistance mechanisms in antitumor therapies

Abstract

Therapeutic resistance remains a major bottleneck in achieving effective antitumor treatment. Many tumors exploit aberrant metabolic behaviors (e.g., excessive glycolysis, oxidative phosphorylation, autophagy, and anabolic pathways) to evade therapy-induced stress and sustain proliferation. Consequently, reprogramming tumor metabolism has emerged as a promising strategy for sensitizing tumors to various treatments. In this review, we outline a nanoplatform-mediated metabolic reprogramming framework as a unifying strategy to reverse diverse resistance mechanisms in tumor therapy. We systematically summarize the recent advances in nanoplatform-based strategies that precisely regulate key metabolic pathways to sensitize tumors to chemotherapy, thermotherapy, reactive oxygen species–based therapies, and immunotherapy. These nanoplatforms integrate metabolic intervention with controlled delivery, offering enhanced therapeutic efficacy, improved selectivity, and reduced systemic toxicity. Furthermore, we discuss the current challenges and opportunities associated with metabolic heterogeneity, biosafety, and clinical translation, highlighting future research directions. This review emphasizes the significance of tumor metabolic reprogramming and provides insights for the rational design of advanced nanoplatforms with strong potential for translational cancer therapy.