Recent advances in nanoscale combination delivery systems for colorectal cancer treatment

Colorectal cancer (CRC) is the third most common cancer worldwide, and its clinical management remains limited by systemic toxicity and drug resistance. Combination regimens can improve therapeutic efficacy through synergistic mechanisms, yet they remain constrained by the divergent physicochemical properties of the paired drugs, inefficient tumor targeting, and asynchronous drug release. Nanoscale co-delivery systems provide an effective strategy to overcome these obstacles. Drawing on a structured literature search, this review synthesizes work published over the past three years on nanoscale co-delivery systems for CRC therapy. These systems are built on organic nanomaterials (liposomes, micelles, and hydrogels) and on inorganic nanomaterials (gold nanoparticles). They achieve efficient tumor accumulation and programmed drug release through two design principles. Targeting ligands, with folate as a representative example, direct the carriers to the tumor, and multi-responsive architectures then release the payload in response to pH, enzymatic activity, and photothermal stimuli. Together, these features enhance synergistic antitumor activity and reduce systemic toxicity. The review then assesses the application potential of nanoscale co-delivery systems in CRC treatment and the principal barriers to their clinical translation. Future directions include designing intelligent carriers through multidisciplinary integration, optimizing combination regimens, and characterizing carrier safety and metabolism. Progress will also depend on pairing co-delivery with immunotherapy and other modalities to improve therapeutic outcomes in CRC.