Image-Guided TME-Improving Nano-Platform for Ca²⁺ Signal Disturbance and Enhanced Tumor PDT

Dysfunction of the calcium balancing system and disruption of calcium distribution can induce abnormal intracellular calcium overload, further causing serious damage and even cell death, which provides a potential therapeutic approach for tumor treatment. Herein, a nano-platform, which includes UCNPs-Ce6@RuR@mSiO₂ @PL-HA NPs (UCRSPH) and SA-CaO₂ nanoparticles, is prepared for improving the tumor micro-environment (TME), Ca²⁺ signal disturbance as well as enhanced photodynamic tumor therapy (PDT). UCRSPH combined with SA-CaO₂ can alter TME and relieve hypoxia of the tumor to realize self-reinforcing PDT under near-IR irradiation (980 nm). The ruthenium red (RuR) in the UCRSPH NPs can be released to the cytoplasm after endocytosis of the nanoparticles, target Ca²⁺ channel proteins on the endoplasmic reticulum and mitochondria, sarcoplasmic reticulum Ca²⁺ -ATPase (SERCA), and mitochondrial calcium uniporter (MCU). The combined participation of nanoparticles and RuR promotes Ca²⁺ imbalance and cytoplasmic calcium overload with the assistance of CaO₂ , and provides tumor cells higher sensitivity to PDT. Furthermore, the nano-platform also provides fluorescence imaging and calcification computed tomography imaging for in vivo treatment guidance. In conclusion, this image-guided nano-platform show potential for highly specific, efficient combined therapy against tumor cells with minimal side-effects to normal cells by integrating TME improvement, self-reinforcing PDT, and Ca²⁺ signal disturbance.