Hypoxia, as a characteristic feature of solid
tumors, has a close relationship with
tumor resistance to
photodynamic therapy (
PDT) and
chemotherapy.
Perfluorocarbon (PFC) is reported to relieve hypoxic in solid
tumors by acting as an
oxygen carrier via several nanostructures. However, the
oxygen delivery process is mostly driven by a concentration gradient, which is uncontrollable. Herein, a photothermally controlled "
oxygen bomb" PSPP-Au980 -D is designed by encapsulating a PFC core within a functionalized bilayer
polymer shell. Near-infrared second window photothermal agent
gold nanorods with excellent photo-to-heat energy-conversion ability are fabricated on the surface of the
polymer shell via an innovative modified two-step seedless ex situ growth process to thermally trigger O2 release. Then, a programmed cascade
therapy strategy is customized for hypoxic orthotopic
pancreatic cancer. First, PSPP-Au980 -D is irradiated by a 980 nm
laser to photothermally trigger O2 infusing into the hypoxic tumor microenvironment, which is accompanied by local
hyperemia and
doxorubicin release. Subsequently, a 680 nm
laser is used to generate
singlet oxygen in the oxygenated tumor microenvironment for
PDT. This choreographed programmed cascade
therapy strategy will provide a new route for suppressing hypoxic
tumor growth under mild conditions based on controllable and effective
oxygen release.