Figure 12.

Benefits of utilizing nanocarriers for isorhamnetin drug delivery in cancer therapy. (A) Isorhamnetin has low systemic availability due to poor water solubility, inadequate absorption, low stability, rapid metabolism, and quick excretion, which diminishes the active drug concentration at tumor sites. The uptake of free isorhamnetin by the tumor cells is also limited, leading to low therapeutic outcomes. (B) Isorhamnetin-loaded, nonfunctionalized nanocarriers improve systemic availability and facilitate higher drug delivery to the tumor microenvironment through the enhanced permeability and retention (EPR) effect, as well as improved cellular penetration, resulting in better therapeutic effects compared to free isorhamnetin. (C) In contrast, ligand-functionalized or surface-engineered nanocarriers achieve greater therapeutic benefits than nonfunctionalized versions owing to their effective entry in more significant quantities into the tumor microenvironment via the EPR effect and targeted delivery to tumor cells, thereby enhancing their therapeutic effectiveness while reducing non-specific interactions toxicity [307,309,352,409,410,411].