NIR-Triggered Intracellular H⁺ Transients for Lamellipodia-Collapsed Antimetastasis and Enhanced Chemodynamic Therapy

In solid tumors, tumor invasion and metastasis account for 90 % of cancer-related deaths. Cell migration is steered by the lamellipodia formed at the leading edge. These lamellipodia can drive the cell body forward by its mechanical deformation regulated by cofilin. Inhibiting cofilin activity can cause significant defects in directional lamellipodia formation and the locomotory capacity of cell invasion, thus contributing to antimetastatic treatment. Herein, a near infrared light (NIR)-controlled nanoscale proton supplier was designed with upconversion nanoparticles (UCNPs) as a core coated in MIL-88B for interior photoacids loading; this photoacids loading can boost H⁺ transients in cells, which converts the cofilin to an inactive form. Strikingly, inactive cofilin loses the ability to mediate lamellipodia deformation for cell migration. Additionally, the iron, which serves as a catalyticaly active center in MIL-88B, initiates an enhanced Fenton reaction due to the increased H⁺ in the tumor, ultimately achieving intensive chemodynamic therapy (CDT). This work provides new insight into H⁺ transients in cells, which not only regulates cofilin protonation for antimetastatic treatment but also improves chemodynamic therapy.