Self-immolative polymer based nanosensitizers enhance antitumor efficacy of sonodynamic therapy
발표자
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초록
내용
Sonodynamic therapy (SDT) is a treatment modality that induces reactive oxygen species (ROS)-mediated cell death. However, the low ROS yield from conventional sonosensitizers has limited the clinical application of SDT. To address this issue, we designed hydrophilized self-immolative polymer-decorated titanium dioxide nanoparticles (HSI-TNPs). The self-immolative polymer (SIP) on the nanoparticle surface rapidly disassembles in response to the hydrogen peroxide-rich cancer cells, subsequently releasing 1,4-quinone methide (QM). This QM alkylates glutathione (GSH), disrupting the redox balance within the cells. In addition, upon exposure to ultrasound, nanoparticles generate a substantial amount of ROS. In tumor-bearing mouse model, HIS-TNPs with SDT successfully inhibited tumor growth through the synergistic effect of glutathione depletion and ROS generation. As a result, HIS-TNPs induces more effective cancer cell killing and significantly improves the therapeutic potential of SDT.