Cancer therapy continues to face significant limitations related to insufficient selectivity, systemic toxicity, and therapeutic resistance, driving growing interest in nanoformulation-based targeted approaches. This review critically synthesizes recent preclinical and clinical evidence on nano-enabled cancer therapies, with a specific focus on delivery systems incorporating either a single therapeutic agent or the co-delivery of multiple agents. Across major cancer types-including lung, breast, prostate, pancreatic, and colorectal cancers-nano-based drug delivery systems demonstrate improved pharmacokinetics, enhanced tumor accumulation, and reduced off-target toxicity. Importantly, our comparative analysis reveals that while single-drug nanoformulations primarily enhance drug stability, bioavailability, and safety, multi-drug nanoformulations more consistently achieve superior therapeutic outcomes by addressing tumor heterogeneity and multidrug resistance through synergistic mechanisms. Distinct from existing reviews that emphasize individual nanocarriers or isolated cancer models, this work provides a cross-cancer, strategy-oriented evaluation of single-agent versus multi-drug nanoformulations. Despite their greater therapeutic promise, multi-drug systems face substantial challenges related to formulation complexity, reproducibility, and clinical translation, underscoring the need for standardized design frameworks and rigorous clinical validation to enable their successful implementation.
Nurdogan et al. (Fri,) studied this question.