An Advanced Nanomedicine Based on Dual Drug-Encapsulated Layered Double Hydroxides for Synergistic Photothermo-Chemotherapy

Developing highly effective nanomedicines for precision therapeutics of nasopharyngeal carcinoma still remains a challenging task. We report here a layered double hydroxide (LDH)-based therapeutic platform for synergistic photothermo-chemotherapy of nasopharyngeal carcinoma. In our approach, we first optimized the synthesis approach and selected a microfluidic method to create homogeneously distributed LDH nanodisks. The created LDHs were then utilized to load dual photothermal drug indocyanine green (ICG) and chemotherapeutic drug toyocamycin (Toy) via electrostatic interaction and hydrogen bonding, respectively. Finally, the dual drug-loaded LDHs were camouflaged with apoptotic cancer cell membranes via physical extrusion to provide cancer cell targeting specificity. The created functional LDH platform exhibits a desired photothermal conversion efficiency (η = 36%) and pH-dependent drug release kinetics and can homologously target cancer cells to induce apoptosis via ICG-mediated photothermal therapy under laser irradiation and Toy-prompted chemotherapy. In addition, a three-dimensional (3D) multicellular tumor spheroid model was established to simulate solid tumors. We show that the functional LDH nanomedicine enables effective tumor penetration, and the efficacy of the combination therapy group is 2.3-fold higher than that of the single-mode Toy-mediated chemotherapy without laser irradiation. These findings suggest that the developed dual drug-encapsulated LDH platform enables synergistic photothermo-chemotherapy, which may be further extended for further in vivo investigations.