Pterostilbene-loaded polymeric nanoparticles: Current status on anticancer activity and the prospect of its stilbene analogues

Cancer remains a leading cause of global mortality, and although chemotherapy, radiotherapy, and surgical interventions constitute standard treatment strategies, their clinical utility is often constrained by systemic toxicity, limited selectivity, and therapeutic resistance. Phytochemicals have emerged as promising anticancer agents due to their multitargeted mechanisms and favorable safety profiles. Among them, pterostilbene (PTE), a naturally occurring stilbenoid, exhibits significant anticancer activity across diverse tumor models through modulation of key oncogenic pathways, including signal transducer and activator of transcription 3 (STAT3), phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (Akt), nuclear factor kappa B (NF-κB), epithelial-mesenchymal transition (EMT), and apoptosis-related signaling. However, its clinical translation is limited by poor aqueous solubility and suboptimal pharmacokinetics. Recent advances in polymeric nanoparticles (PNPs) engineering have provided viable strategies to enhance the therapeutic potential of PTE. Reported PTE-loaded PNPs generally exhibit particle sizes within the optimal 90–200 nm range and high encapsulation efficiencies, contributing to improved cellular uptake and tumor accumulation. Comparative evaluation indicates that ligand-functionalized and stimuli-responsive systems achieve the most pronounced reductions in half-maximal inhibitory concentration (IC 50 ) values and superior in vivo tumor inhibition, whereas PEG-based platforms primarily improve pharmacokinetic profiles and survival outcomes. This review critically synthesizes the molecular anticancer mechanisms of PTE and evaluates the design, performance, and translational prospects of polymeric nanoparticle delivery systems, highlighting nanoformulation as a promising strategy to advance stilbenoid-based therapeutics toward clinical application.