Hollow Cavity CaO₂ @Polydopamine Nanocomposites for pH-Responsive Ca²⁺ -Enhanced Efficient Mild Hyperthermia in the...

Second near-infrared (NIR-II) mild photothermal therapy with higher tissue penetration depth and less damage to healthy tissues is emerging as an attractive antitumor modality, but its therapeutic efficiency is dramatically suppressed by the resistance of heat shock proteins (HSPs). As a widely explored photothermal agent, the application of polydopamine (PDA) in the NIR-II region is hampered by low photothermal conversion efficiency (PCE). Herein, its PCE in the NIR-II region is improved by developing novel hollow cavity CaO₂ @PDA nanocomposites through chelation-induced diffusion of inner core Ca²⁺ to the shell PDA to facilitate multiple reflections of laser in the cavity. Upon pH-responsive degradation of CaO₂ , its structure is transformed into a stacked "nano-mesh" with excellent light absorption and an enlarged effective irradiation area. Overloading of Ca²⁺ ions not only induces downregulation of HSPs but also enhances interference of light on membrane potential, which further aggravate mitochondrial dysfunction and reduce the thermotolerance of tumor cells, promoting efficient mild hyperthermia of PDA in the NIR-II region.