Lamellar Metal Oxide Based Nanoagent Realizing Intensive Interlamellar Ca2+ Release and Hypoxia Relief for Enhanced Synergistic Therapy

As an emerging cancer treatment, Ca2+-loaded nanoagents can disorder intracellular calcium homeostasis to induce cancer cell death. However, the developed Ca2+ nanocarriers are very limited in variety. Herein, we developed a metal oxide based nanoagent, Ca0.35CoO2@ss-SiO2-Ce6 (denoted as CCO@ss-SiO2-Ce6), which not only intensively released Ca2+ but also realized enhanced photothermal and photodynamic therapy. The excellent photothermal conversion efficacy (48.01% at 808 nm laser illumination, 1 W/cm2), high heat-enhanced release rate of Ca2+ (50.09% at pH 4.5), and catalase-mimic activity to generate oxygen as well as the facilitated production of the singlet oxygen all contributed to the enhanced synergistic cancer therapy efficacy. The in vitro and in vivo experiments displayed that CCO@ss-SiO2-Ce6 demonstrated superior biocompatibility and remarkable suppressive tumor growth. This work opens a pathway for fabricating synergistic therapeutic nanoplatforms.