Nanomedicines for combining chemotherapy and sonodynamic
therapy
(SDT) have enormous potential in squamous cell carcinoma treatment.
However, the therapeutic efficacy of noninvasive SDT is severely limited
because the generation of reactive oxygen species (ROS) by sonosensitizers
is highly dependent on the levels of intracellular excess glutathione
(GSH) in the tumor cells. To overcome this barrier, a red blood cell
(RBC) membrane-camouflaged nanomedicine consisting of GSH-sensitive
polyphosphoester (SS-PPE) and ROS-sensitive polyphosphoester (S-PPE)
was designed for the simultaneous delivery of the sonosensitizer hematoporphyrin
(HMME) and chemotherapeutic agent docetaxel (DTXL) for effectively
enhanced antitumor efficacy. In vitro and in vivo studies demonstrated that HMME-driven ROS generation
under ultrasound (US) inhibited SCC7 cell proliferation and accelerated
DTXL release to further kill tumor cells via the
hydrophobic–hydrophilic transition of the nanoparticle core.
Meanwhile, the disulfide bond of SS-PPE effectively consumes GSH to
prevent ROS consumption. This biomimetic nanomedicine provides GSH
depletion and amplified ROS generation capabilities to achieve a novel
synergistic chemo-SDT strategy for squamous cell carcinomas.
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