Multi-target saponins in cancer therapy: Direct binding mechanisms and lipid-based nanoparticles as a synergistic solution

초록

Saponins are plant-derived amphiphilic glycosides with notable anticancer effects. Specific triterpenoids and steroidal saponins directly bind to various molecular factors, with several interactions validated by techniques, such as surface plasmon resonance and microscale thermophoresis. Through these interactions, saponins modulate key signaling cascades, including PI3K/Akt, MAPK, and Wnt/β-catenin pathways, thereby exerting anticancer activities. Therefore, they have emerged as promising candidates for the development of multi-target anticancer drugs. However, their therapeutic applications are limited by their poor oral bioavailability, membrane-disruptive toxicity, and formulation instability. Lipid-based nanoparticles (LBNPs) provide strategic solutions to these challenges. In addition to serving as delivery platforms, LBNPs and saponins form a mutually synergistic system. While LBNPs enhance the stability, absorption, and tissue-specific delivery of saponins, saponins themselves stabilize LBNPs, promote endosomal escape, and increase cellular uptake. This bidirectional interaction is a novel paradigm in nanomedicine. This review presents an integrated analysis of the interactions between saponins and their targets, and the enhancement of their delivery by LBNPs, providing a framework for co-engineering self-synergizing, multi-target nanotherapeutics. By bridging mechanistic pharmacology with delivery innovation, this study offers strategic insights into overcoming the barriers to saponin-based drug development and advancing next-generation anticancer therapies.

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