Nanomaterials for Targeting the Golgi Apparatus in Cancer

Abstract The Golgi apparatus (GA) is a central regulator of protein processing, glycosylation, trafficking, secretion, and cellular signaling, which are frequently dysregulated in cancer. Structural and functional alterations of the Golgi apparatus support tumor proliferation, invasion, metastasis, immune evasion, and therapeutic resistance. Key Golgi-associated processes, including aberrant glycosylation, altered secretory pathways, and overexpression of oncogenic proteins, contributev significantly to cancer progression. Given its critical role in tumor biology, the Golgi apparatus has emerged as a promising yet underexplored therapeutic target. Unlike conventional organelle-targeted strategies that focus on the nucleus, mitochondria, or endoplasmic reticulum, Golgi-directed therapies can simultaneously disrupt protein secretion, receptor maturation, intracellular trafficking, and oncogenic signaling, thereby impairing multiple cancer-promoting pathways. One of the major challenges in Golgi-targeted cancer therapy is selective and specific targeting of the Golgi apparatus in tumor tissues, keeping healthy tissues untouched. In this regard, nanoplatforms have emerged as one of the strategies to overcome these problems. In this review, we discuss the recent advances in nanomedicine which enabled the development of diverse Golgi-targeting platforms, including carbon- and graphene-based nanomaterials, lipid and protein nanoparticles, self-assembled nanostructures, cell membrane-coated nanoparticles, metallic nanoparticles, and photosensitizer-based systems. These nanomaterials employ Golgi-localizing ligands and biomolecular targeting strategies to deliver therapeutic cargo to the Golgi apparatus, inducing organelle dysfunction through a myriad of mechanisms. Despite significant progress, major challenges remain, such as limited organelle selectivity, complex multistep nanomaterial synthesis and scalability, as well as insufficient understanding of Golgi-specific therapeutic mechanisms. We also focused on the development of potential solutions to these challenges toward efficient translation of Golgi-targeted nanomedicines and established the Golgi apparatus as a powerful therapeutic target in next-generation precision cancer treatment.