Engineered MOF-5-based Nanocomposites for Advanced Tumor Combinational Therapy by Ultrasound/Laser Actuation: A Comparison on Anti-tumor Elucidations

Exploring and optimizing antitumor therapeutic strategies remains challenging but critical for future clinical translations. To this end, this study reported a type of engineered metal-organic framework-5 (MOF-5)-based nanosheet composite (MOF-5@ICG-HA/MOF-5@RB-HA, MIH/MRH) as well as their ultrasound (US)/laser actuation for reactive oxygen species (ROS) production and subsequent piezo/pyroelectric dynamic therapies. Mesoporous MOF-5 nanosheets were loaded with rose bengal (RB) or indocyanine green (ICG), followed by surface modification with hyaluronic acid (HA). Systematic physiochemical characterizations revealed that their energy band structure in conjunction with the mesoporous architecture promoted ROS generation and diffusion at the presence of US/laser actuation. Cellular uptake demonstrated that the HA-tag endowed these nanocomposites with specific binding capability to CD44 receptors on A549 cell. Upon US or laser actuation, these engineered nanocomposites exhibited remarkable tumor cell apoptosis in vitro due to the superb piezo/pyroelectric dynamic effects, and displayed excellent tumor inhibition rates (up to 92.8%) in vivo. Notably, the US-laser dual-actuated group demonstrated a significantly enhanced therapeutic performance with a tumor inhibition rate of 95.6%, which highlighted a marked advantage of combined actuations. Overall, these MOF-5-based nanocomposites have provided a promising strategy for effective combined A549 tumor therapy, and exhibited favorable prospects for clinical translation using commercial medical sono/photo-devices.