In:
Angewandte Chemie International Edition, Wiley, Vol. 60, No. 17 ( 2021-04-19), p. 9562-9572
Kurzfassung:
Chemodynamic therapy is an emerging tumor therapeutic strategy. However, the anticancer effects are greatly limited by the strong acidity requirements for effective Fenton‐like reaction, and the inevitably “off‐target” toxicity. Herein, we develop an acidity‐unlocked nanoplatform (FePt@FeO x @TAM‐PEG) that can accurately perform the high‐efficient and tumor‐specific catalysis for anticancer treatment, through dual pathway of cyclic amplification strategy. Notably, the pH‐responsive peculiarity of tamoxifen (TAM) drug allows for the catalytic activity of FePt@FeO x to be “turn‐on” in acidic tumor microenvironments, while keeping silence in neutral condition. Importantly, the released TAM within cancer cells is able to inhibit mitochondrial complex I, leading to the upregulated lactate content and thereby the accumulated intracellular H + , which can overcome the intrinsically insufficient acidity of tumor. Through the positive feedback loop, large amount of active FePt@FeO x nanocatalyzers are released and able to access to the endogenous H 2 O 2 , exerting the improved Fenton‐like reaction within the more acidic condition. Finally, such smart nanoplatform enables self‐boosting generation of reactive oxygen species (ROS) and induces strong intracellular oxidative stress, leading to the substantial anticancer outcomes in vivo, which may provide a new insight for tumor‐specific cascade catalytic therapy and reducing the “off‐target” toxicity to surrounding normal tissues.
Materialart:
Online-Ressource
ISSN:
1433-7851
,
1521-3773
DOI:
10.1002/anie.202014415
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2021
ZDB Id:
2011836-3
ZDB Id:
123227-7
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