Current methodologies to refine bioavailability, delivery, and therapeutic efficacy of plant flavonoids in cancer treatment.

Abstract Over the last two decades, several advancements have been made to improve the therapeutic efficacy of plant flavonoids, especially in cancer treatment. Factors such as low bioavailability, poor flavonoid stability and solubility, ineffective targeted delivery, and chemo-resistance hinder the application of flavonoids in anticancer therapy. Many anticancer compounds failed in the clinical trials because of unexpected altered clearance of flavonoids, poor absorption after administration, low efficacy, and/or adverse effects. Hence, the current research strategies are focused on improving the therapeutic efficacy of plant flavonoids, especially by enhancing their bioavailability through combination therapy, engineering gut microbiota, regulating flavonoids interaction with ATP-binding cassette (ABC) efflux transporters, and efficient delivery using nanocrystal and encapsulation technologies. This review aims to discuss different methodologies with examples from reported dietary flavonoids that showed an enhanced anticancer efficacy in both in vitro and in vivo models. Further, the review discusses the recent progress in biochemical modifications of flavonoids to improve bioavailability, solubility, and therapeutic efficacy.