The Translational Paradox of Cancer Nanomedicine: Biological, Pharmacokinetic, and Manufacturing Barriers to Clinical Success
Simple Summary Nanomedicine uses extremely small carriers to transport anticancer drugs through the body and, in principle, deliver them more selectively to tumors. Although many such systems perform very well in laboratory experiments and animal studies, only a limited number have produced clear and lasting benefits for patients. This review explains why this gap persists. After entering the bloodstream, nanoparticles can acquire a new biological coating, be removed by the immune system, accumulate in healthy organs, or fail to penetrate the complex and highly variable structure of human tumors. Their performance may also change during large-scale production, while differences among patients further reduce the predictability of treatment outcomes. The review also examines the clinical experience with approved, unsuccessful, and discontinued cancer nanomedicines. More reliable progress will require designs based on biological mechanisms, human-relevant experimental models, consistent manufacturing and testing standards, and clinical trials that select patients using measurable biological features indicating who is most likely to benefit. Addressing these challenges may help transform promising laboratory technologies into safer and more effective cancer treatments.