Advancing Cancer-Targeted Nanotherapies with Tumor Homing Peptides.

The development of smart nanoparticles for precision medicine in anticancer drug delivery and controlled release has the potential to revolutionize cancer treatment. This progress is driven by expanding body of preclinical and early clinical studies on anticancer nanoparticles. Despite these advancements, a critical challenge remains achieving a selective and efficient tumor accumulation, along with effective extravasation and deep tissue penetration of nanoparticles into the tumor parenchyma. Affinity targeting strategies using ligands such as homing peptides and antibodies leverage molecular recognition to enhance selectivity, efficacy, and therapeutic activity by directing them to tumor-specific receptors or biomarkers, thereby minimizing off-target effects and improving drug delivery efficiency. Tumor-homing C-end Rule (CendR) peptides, such as prototypic iRGD peptide, represent a promising strategy due to their unique multistep mechanism that facilitates both selective targeting and enhanced tissue penetration. This review highlights key milestones in the evolution of peptide-targeted nanoparticles, underscoring their role in advancing precision nanomedicine.