Introduction: Skin cancer is a major global health concern, with rising prevalence and limited effectiveness of conventional therapies. Natural phytopharmaceuticals, particularly those derived from Triticum aestivum (wheatgrass), offer promising therapeutic potential due to their antioxidant, anti-inflammatory, and anticancer properties. This review explores the potential of nanogel-encapsulated wheatgrass bioactives to modulate molecular pathways involved in skin cancer development. Methods: A comprehensive review was conducted of preclinical studies, advances in nanogel-based delivery systems, and the molecular pharmacology of wheatgrass phytoconstituents. Emphasis was placed on their interactions with key cancer-related signaling pathways and the impact of nanogels on pharmacokinetic and pharmacodynamic profiles. Results: Wheatgrass bioactives were found to regulate oncogenic pathways, including PI3K/Akt, MAPK/ERK, NF-κB, and p53. Nanogel encapsulation enhanced solubility, stability, targeted delivery, and bioavailability. Both in vitro and in vivo studies demonstrated improved cytotoxicity against melanoma and non-melanoma skin cancer cells, with reduced off-target effects. Discussion: Nanogel-based delivery of wheatgrass phytopharmaceuticals offers a multi-targeted strategy by modulating multiple cancer pathways while addressing challenges associated with natural compound delivery. Despite promising preclinical results, translational limitations remain, including scarce human trials and variability in formulation. Future research should prioritize clinical validation and regulatory standardization. Conclusion: Nanogel-encapsulated wheatgrass bioactives represent a novel, mechanism-driven, and targetspecific approach for skin cancer therapy, with the potential to advance phytotherapy toward mainstream oncology treatment.
Singh et al. (Mon,) studied this question.