In addition, albumin nanoparticles can bypass the hENT1-dependent uptake pathway due to their natural targeting (binding to the tumor microenvironment through SPARC protein) and unique transmembrane mechanisms (such as gp60 receptor mediated transport), directly increasing the concentration of gemcitabine in resistant tumor cells, and have shown advantages in overcoming hENT1-deficient resistance in pancreatic cancer and bladder cancer models (Bartkowski et al., 2024; Liu et al., 2025). This evidence concerns the gene SPARC and neoplasm.