Coordination self-assembly of natural flavonoids into robust nanoparticles for enhanced in vitro chemo and photothermal cancer therapy

Utilizing small natural molecules from traditional Chinese medicines is highly promising and advantageous in curing diverse diseases. However, the clinical translation of many of these molecular drugs was hindered due to the vulnerable chemical structure and poor solubility. Herein, we reported a coordination-driven assembly strategy to synchronously enhance the stability and solubility of a typical natural molecular drug (luteolin) through the formation of nanoparticles. The resulting nanoparticles showed much enhanced solubility in physiological environment, broadened absorption spectrum to the near-infrared region, and high stability against oxidation. Intriguingly, the coordinated assembly with ferric ion introduces the supramolecular photothermal effects, enabling the nanoparticles to act as either a chemotherapeutic agent or a photothermal agent. This work represents that the coordination assembly strategy is facile and efficient for design of nanodrugs starting from naturally-derived molecular drugs and greatly enhance their therapeutic efficacy.