pH-Responsive Multifunctional Nanoplatforms with Reactive Oxygen Species-Controlled Release of CO for Enhanced Oncotherapy.

Recently, various nanomaterials have drawn increasing attention for enhanced tumor therapy. However, a lack of tumor uptake and insufficient generation of cytotoxic agents have largely limited the antitumor efficacy in vivo. Herein, a multifunctional nanoplatform (IL@CPPor(CO)) was constructed with pH-responsive copper peroxide nanoparticles (CPNP) that are capable of self-supplying H 2 O 2 , a radical-sensitive carbonic oxide (CO) donor (Fe 3 (CO) 12 ), photosensitizer Iridium(III) meso-tetra ( N -methyl-4-pyridyl)porphyrin pentachloride (IrPor), and ionic liquid (IL) for enhanced oncotherapy. Under acidic conditions, the CPNP could decompose to release H 2 O 2 and Cu 2+ . The concomitant generation of H 2 O 2 could efficiently trigger Fe 3 (CO) 12 to release the CO in situ. On the other hand, Cu 2+ possesses both glutathione depletion and Fenton-like properties. In addition, IrPor has both peroxidase-like activity and photosensitizer properties to produce reactive oxygen species (ROS) in tumors. The released ROS could trigger the rapid intracellular release of CO. More importantly, released CO and ROS could promote cell apoptosis and improve the therapeutic efficacy. Moreover, due to the pH-dependent ROS generation property, the IL@CPPor(CO) exhibited high tumor accumulation, low toxicity, and good biocompatibility, which enabled effective tumor growth inhibition with minimal side effects in vivo. This work provides a novel multifunctional nanoplatform that combined photodynamic therapy with CDT and CO to improve therapeutic efficacy.