Glucose transporter 1 (GLUT1)-targeting and hypoxia-activated mitochondria-specific chemo-thermal therapy via a glycosylated poly(amido amine)/celastrol (PAMAM/Cel) complex

Schematic illustration of the design principle of the Glu-PEG-Azo/Mito-Cel808 complex and its action mechanism about inhibiting tumor growth and metastasis. The complex could be actively transported by GLUT1-overexpressing tumor cell. Subsequently, mitochondrial targeting was activated when PEG detached from PAMAM stimulated by the hypoxic tumor microenvironment. Finally, the tumor mitochondria were completely destroyed after Cel were rapidly released in the alkaline mitochondrial matrix and IR808 produced great heat with laser irradiation. Thus, the complex possessed superior specificity and efficiency in inhibiting tumor growth and metastasis.