Versatile carrier-free binary nanodrug based on metformin/epigallocatechin gallate nanoparticles: exploring its properties and potential in cancer treatment†

Epigallocatechin gallate (EGCG), an important active component extracted from green tea, has attracted much attention due to its multiple biological activities such as antioxidant, antibacterial, anti-inflammatory, and antitumor effects. Meanwhile, metformin (Met), a classic drug for the treatment of type 2 diabetes, exhibits additional benefits such as hypoglycemic, antioxidant, anti-inflammatory, and antitumor effects. However, metformin often causes gastrointestinal reactions when used alone, affecting patients’ quality of life. In view of this, we proposed an innovative technique for the fabrication of a carrier-free, dual-loaded nanodrug, Met-EGCG nanoparticles (Met-EGCG NPs), via self-assembly. The method for preparing Met-EGCG NPs is simple, rapid and cost-effective. In addition, the carrier-free Met-EGCG NPs nanodrug inherits the strong antioxidant capacity, good biocompatibility and excellent aggregation-induced fluorescence effect of EGCG, and even offer significant advantages in enhancing drug solubility, stability, and bioavailability, while effectively reducing the occurrence of side effects. Moreover, this Met-EGCG NPs nanodrug exhibits a synergistic therapeutic effect of EGCG and metformin, thereby significantly enhancing overall therapeutic efficacy, and demonstrates excellent potential in anti-cancer applications. This study not only successfully prepared Met-EGCG NPs but also experimentally verified their superior performance, opening a new path for the application of EGCG in drug therapy. This carrier-free, dual-loaded drug delivery nanosystem based on Met-EGCG NPs offers potential for drug combination therapy, promising to play a more critical role in the biomedical field and providing new insights and guidance for the development of future multidrug delivery systems.