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. The complexity of pancreatic cancer treatment with its unique avascular and protective stromal barrier, poses challenges in reaching the tumor region – necessitating advanced combination therapy. While polymeric drug delivery carriers for combination chemotherapy have been developed through the synthesis of amphiphilic polymers, this process can be time-consuming and laborious. Polymer entanglement-based drug encapsulation has been limited in achieving high drug encapsulation efficiency because of the intrinsic preference for the localization or encapsulation of drugs based on their polarity. Herein a novel approach was employed, utilizing dynamic bonding and supramolecular assembly at the oil/water interface for drug encapsulation. An emulsion interface was formulated by metal-phenolic coordinate bonds, stabilizing nanoemulsions with diameters ranging from 50 to 100 nm for three weeks. These nanoemulsions co-encapsulated hydrophilic (gemcitabine) and hydrophobic (paclitaxel) anticancer drugs. Moreover, the cellular toxicity of the dual drugs-encapsulated nanoemulsions treatment showed better toxicity (57.0 ± 0.0%) than that of the gemcitabine only-encapsulated (84.0 ± 9.9%) and paclitaxel only-encapsulated (83.4 ± 7.2%) nanoemulsion treatments, demonstrating the potential of multidrug delivery carriers for synergistic combination therapy.