The unique tumor microenvironment
(TME) characteristic of severe
hypoxia, overexpressed intracellular glutathione (GSH), and elevated
hydrogen peroxide (H2O2) concentration limit
the anticancer effect by monotherapy. In this report, glucose oxidase
(GOx)-encapsulated mesoporous hollow Co9S8 nanoreactors
are constructed with the coverage of polyphenol diblock polymers containing
poly(oligo(ethylene glycol) methacrylate) and dopamine moieties containing
methacrylate polymeric block, which are termed as GOx@PCoS. After
intravenous injection, tumor accumulation, and cellular uptake, GOx@PCoS
deplete GSH by Co3+ ions. GOx inside the nanoreactors produce
H2O2 via oxidation of glucose to enhance •OH-based
chemodynamic therapy (CDT) through the Fenton-like reaction under
the catalysis of Co2+. Moreover, Co3+ ions possess
catalase activity to catalyze production of O2 from H2O2 to relieve tumor hypoxia. Upon 808 nm laser
irradiation, GOx@PCoS exhibit photothermal and photodynamic effects
with a high photothermal conversion efficiency (45.06%) and generation
capacity of the toxic superoxide anion (•O2
–) for photothermal therapy (PTT) and photodynamic therapy
(PDT). The synergetic antitumor effects can be realized by GSH depletion,
starvation, and combined CDT, PTT, and PDT with enhanced efficacy.
Notably, GOx@PCoS can also be used as a magnetic resonance imaging
(MRI) contrast agent to monitor the antitumor performance. Thus, GOx@PCoS
show great potentials to effectively modulate TME and perform synergistic
multimodal therapy.