Metal-Phenolic Coordination mediated Nanoemulsions for All-in-One Drug Delivery

Abstract

Combination chemotherapy is a promising strategy for cancer treatment, enhancing antitumor efficacy while minimizing drug resistance and mitigating the risk of single-drug overdose toxicity. Polymeric drug delivery carriers for combination chemotherapy have been developed; however, the synthetic process of amphiphilic polymers is time-consuming and laborious. The polymer entanglement-based drug encapsulation has been limited in achieving a high multidrug encapsulation efficiency because of the intrinsic preference for encapsulation of drugs upon their polarity. Herein, inspired by dynamic bonding and supramolecular assembly of metal-phenolic coordinate bonds at the oil/water interface, nanoemulsions were fabricated via a dropwise emulsion process. The emulsion interface was formulated by the coordinate bonds and created a colloidally stable emulsion with 50-100 nm in diameter for 3 weeks. These nanoemulsions enabled the coencapsulation of anticancer drugs, hydrophilic gemcitabine, and hydrophobic paclitaxel. Moreover, the treatment of dual-drug-encapsulated nanoemulsions reduced cellular viability (57.0 ± 0.0%) compared to that of gemcitabine only encapsulated (84.0 ± 9.9%) and paclitaxel only encapsulated (83.4 ± 7.2%) nanoemulsion treatment, demonstrating the potential of multidrug delivery carriers for synergistic combination therapy. © 2025 American Chemical Society.