Cancer is still a major threat to human health at present. Developing new types of integrated nanoplatforms for the accurate diagnosis and effective treatment of
cancer is very significant. Herein, an intelligent dual-stage core-shell
cancer theranostic nanoplatform (Fe3+@Au1Ag24@PbP) with NIR
laser/tumor-microenvironment (TME) co-responsiveness and multi-modal imaging-
therapy was successfully prepared, which was composed of the precisely structured oil-soluble Au1Ag24 nanoclusters (NCs) and Fe3+
ions easily assembled within the oil and aqueous phases of the
polyethylene glycol (PEG) block grafted polyketal (PK) copolymer (PK-b-PEG, PbP) vesicles, respectively. In this system, we were delighted to find that the prepared Au1Ag24 NCs possess multi-photoresponsive properties, endowing the nanoplatform with photoacoustic (PA)/photothermal (PT) imaging and synergetic
photothermal therapy (PTT)/
photodynamic therapy (
PDT) for
cancer under near-infrared (NIR)
laser irradiation. On the other hand, Fe3+
ions exhibit multi-TME response and regulation behaviors, including as catalysts for the decomposition of endogenous
hydrogen peroxide (H2O2) in the solid
tumor to produce O2 and as the
oxidizing agent for the consumption of the intracellular GSH to avoid the reduction of the generated 1O2; therefore, the synchronously formed Fe2+
ions from the redox of Fe3+ with GSH could further react with H2O2 to produce
hydroxyl radical (˙OH), which induced ferroptosis-based
cancer treatment. The PbP shell possesses TME/pH sensitivity for controlled drug release and passive targeting, causing a large increase in Au1Ag24/Fe3+ accumulation within the weakly acidic
tumor region and reducing the side effects on normal tissues. Both in vitro and in vivo experiments demonstrate that the Fe3+@Au1Ag24@PbP nanoplatform presented excellent PA/PT imaging-guided synergetic PTT/
PDT/ferroptosis effects toward
tumor cells and
tumors. This integrating multi-responsive and multi-modal
theranostic nanoplatform paves a new way for effective
cancer therapy.