An ultrasound-activatable platinum prodrug for sono-sensitized chemotherapy
Menée à l'aide de lignées cellulaires, de sphéroïdes et de modèles murins de tumeurs, cette étude met en évidence l'intérêt théranostique d'un pro-médicament (cyanineplatine) pouvant être activé et contrôlé de manière spatiotemporelle par les ultrasons
Despite the great success achieved by photoactivated chemotherapy, eradicating deep tumors using external sources with high tissue penetration depth remains a challenge. Here, we present cyaninplatin, a paradigm of Pt(IV) anticancer prodrug that can be activated by ultrasound in a precise and spatiotemporally controllable manner. Upon sono-activation, mitochondria-accumulated cyaninplatin exhibits strengthened mitochondrial DNA damage and cell killing efficiency, and the prodrug overcomes drug resistance as a consequence of combined effects from released Pt(II) chemotherapeutics, the depletion of intracellular reductants, and the burst of reactive oxygen species, which gives rise to a therapeutic approach, namely sono-sensitized chemotherapy (SSCT). Guided by high-resolution ultrasound, optical, and photoacoustic imaging modalities, cyaninplatin realizes the overall theranostics of tumors in vivo with superior efficacy and biosafety. This work highlights the practical utility of ultrasound to precisely activate Pt(IV) anticancer prodrugs for the eradication of deep tumor lesions and broadens the biomedical uses of Pt coordination complexes. A sono-activatable Pt(IV) anticancer prodrug can achieve the on-demand activation of platinum chemotherapeutics in deep tumor.