Research progress of gambogic acid-loaded nanoformulations in tumor therapy
Gambogic acid (GA), a natural xanthone derived from Garcinia plants, exhibits potent broad-spectrum antitumor activity through multiple mechanisms, including apoptosis induction, cell cycle arrest, angiogenesis inhibition, and ferroptosis/pyroptosis triggering. However, its clinical translation is severely hampered by poor water solubility, low bioavailability, rapid metabolism, short half-life, and significant off-target toxicity. Nanotechnology offers a promising solution to overcome these limitations. Nanoparticle-based delivery systems can enhance GA's solubility, extend its circulation time, improve tumor targeting via passive (enhanced permeability and retention effect) or active (ligand-mediated) strategies, and reduce systemic side effects. This review systematically evaluates recent advances in GA-loaded nanoformulations for cancer therapy, covering diverse nanocarrier types (lipid-based, polymeric, inorganic, biomimetic, and metal-coordinated systems), design strategies to address GA's application bottlenecks (e.g., solubilization, long-circulation, smart-responsive release, active targeting), and their therapeutic efficacy in various tumor models. Furthermore, emerging combination therapies integrating GA with chemotherapy, photothermal therapy, or immunotherapy are discussed. The goal is to provide a comprehensive reference for leveraging nanomedicine to unlock the full clinical potential of GA.