Nanomaterial-driven spatiotemporal autophagy modulation: The dual-edged sword in precision cancer therapy

Autophagy-modulating nanomaterials have emerged as a promising therapeutic paradigm in oncology, offering precise intervention in tumor progression, metastasis, and treatment resistance. The therapeutic efficacy of these platforms is largely attributed to their context-dependent dual functionality. On one hand, they are capable of inducing cytotoxic autophagy, such as through the activation of oxidative stress or endoplasmic reticulum stress, leading to tumor cell death. On the other hand, they can inhibit cytoprotective autophagy, a crucial survival mechanism exploited by tumor cells, by impairing lysosomal function or perturbing cellular energy metabolism. A key advancement in this field is the ability of nanomaterials to achieve spatiotemporal control over autophagy modulation, allowing targeted regulation at specific tumor sites and disease stages. This review systematically summarizes the molecular mechanisms underlying these bidirectional effects, with particular emphasis on the modulation of selective autophagy pathways including mitophagy, and discusses how rational nanomaterial design adapted to tumor stage and microenvironment dictates therapeutic outcomes. Finally, we highlight major translational challenges, especially the lack of standardized characterization and the difficulty in precisely controlling autophagic responses, which must be addressed to facilitate the clinical translation of these innovative nanotherapeutic strategies.