To improve the efficiency of radiation therapy (RT) for
breast
cancer, a designable multifunctional core–shell nanocomposite
of FeP@Pt is constructed using Fe(III)-polydopamine (denoted as FeP)
as the core and platinum particles (Pt) as the shell. The hybrid structure
is further covered with hyaluronic acid (HA) to give the final nanoplatform
of FeP@Pt@HA (denoted as FPH). FPH exhibits
good biological stability, prolongs blood circulation time, and is
simultaneously endowed with tumor-targeting ability. With CD44-mediated
endocytosis of HA, FPH can be internalized by cancer
cells and activated by the tumor microenvironment (TME). The redox
reaction between Fe3+ in FPH and endogenous
glutathione (GSH) or/and hydrogen peroxide (H2O2) initiates ferroptosis therapy by promoting GSH exhaustion and •OH
generation. Moreover, FPH has excellent photothermal
conversion efficiency and can absorb near-infrared laser energy to
promote the above catalytic reaction as well as to achieve photothermal
therapy (PTT). Ferroptosis therapy and PTT are further accompanied
by the catalase activity of Pt nanoshells to accelerate O2 production and the high X-ray attenuation coefficient of Pt for
enhanced radiotherapy (RT). Apart from the therapeutic modalities, FPH exhibits dual-modal contrast enhancement in infrared (IR)
thermal imaging and computed tomography (CT) imaging, offering potential
in imaging-guided cancer therapy. In this article, the nanoplatform
can remodel the TME through the production of O2, GSH-
and H2O2-depletion, coenhanced PTT, ferroptosis,
and RT. This multimodal nanoplatform is anticipated to shed light
on the design of TME-activatable materials to enhance the synergism
of treatment results and enable the establishment of efficient nanomedicine.
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