Co-loading of coralyne and indocyanine green into adenine DNA-functionalized mesoporous silica nanoparticles for pH- and near-infrared-responsive chemothermal treatment of cancer cells.

Despite remarkable progress in the construction of functional mesoporous silica nanoparticles (MSNs) for cancer therapy, a multifunctional system with synergistic advantages over any single model remains encouraging. The objective of the present study was to develop a novel, simple and powerful nanotherapeutic system for the pH- and near-infrared (NIR)-responsive chemothermal treatment of cancer cells by co-loading coralyne and indocyanine green (ICG) into the adenine DNA (poly(A))-functionalized MSN. Coralyne, a type of planar alkaloid for cancer chemotherapy, can not only be loaded into the pores of MSN, but can also bind poly(A) and trigger the formation of non-Watson-Crick secondary structures, resulting in pore capping by the cooperative binding of poly(A) strands. Under low-pH or high-temperature conditions, non-Watson-Crick secondary structures were unstable, leading to the dehybridization of the cooperative binding structure and open-gate state. ICG, another cargo co-loaded into MSN, showed high efficiency for the conversion of NIR light into heat, which could provide the fundamental basis of hyperthermal therapy and promote pore opening upon NIR irradiation. In vitro studies using human hepatoma (HepG-2) cells demonstrated that this system could perform well in cellular acidic environment and under NIR irradiation, leading to a significant efficiency in controlled drug release and chemothermal cancer treatment. We believe that with these excellent features it should become a favorable nanoplatform for biomedical applications.