Radiation therapy (RT) has emerged as one of the most promising anti-
tumor strategies for
neuroblastoma. Nevertheless, the special tumor microenvironment (TME), including hypoxic and GSH-overexpressed TME, often greatly restricts the RT outcome. In this study, we demonstrated a dual-channel parallel radicals nanoamplifier (ATO@PAE-PEG-
AS1411/Fe3+). The nanoamplifier was shaped into a bilayer shell-core structure, in which
atovaquone-loaded poly (β-amino
esters)-poly (
ethylene glycol) (ATO@PAE-PEG) served as the core while Fe3+-absorbed
AS1411 aptamer (
AS1411/Fe3+) served as the shell. Taking advantage of the targeting ability of
AS1411, ATO@PAE-PEG-
AS1411/Fe3+ specifically accumulated in
tumor cells, and then released ATO as well as Fe3+ in response to the acidic TME. The released ATO dramatically inhibited the mitochondrial respiration of
tumor cells, thus sparing vast amounts of
oxygen for the generation of
free radicals during RT process, which was the first
free radicals-amplifying pathway Meanwhile, the released Fe3+ could consume the
tumor-overexpressed GSH through the redox reaction, thus effectively preserving the generated
free radicals in RT process, which was the second
free radicals-amplifying pathway. Taken together, our study demonstrates a dual-channel parallel
free radicals-amplifying RT strategy, and it is expected this work will promote the clinical application prospects of RT treatment against
neuroblastoma.