NIR‐Actuated Remote Activation of Ferroptosis in Target Tumor Cells through a Photothermally Responsive Iron‐Chelated Biopolymer Nanoplatform

Abstract

Ferroptosis is anew form of regulated cell death that shows promise for tumor treatment. Most current ferroptosis tumor therapies are based on the intrinsic pathological features of the malignancies,and it would be of clinical significance to develop ferroptosis-inducing strategies with improved tumor specificity and modulability.Here we report ap olydopaminebased nanoplatform (Fe II PDA@LAP-PEG-cRGD) for the efficient loading of Fe 2+ and b-lapachone (LAP), which could readily initiate ferroptosis in tumor cells upon treatment with near-infrared light. PDAn anostructures could generate mild hyperthermia under NIR irritation and trigger the release of the ferroptosis-inducing Fe 2+ ions.T he NIR-actuated photothermal effect would also activate cellular heat shock response and upregulate the downstream NQO1 via HSP70/NQO1 axis to facilitate bioreduction of the concurrently released b-lapachone and enhance intracellular H 2 O 2 formation to promote the Fe 2+-mediated lipid peroxidation.

Emerging roles of ferroptosis in the tumor immune landscape: from danger signals to anti‐tumor immunity

“…DOX could amplify the efficacy of Fe 2+ -mediated ferroptosis by enhancing H 2 O 2 production via NOX4 signaling [60]. We also developed a strategy to combine Fe 2+ and β-lapachone (LAP) to trigger ferroptosis of tumor cells via remotely-controllable near-infrared light [61]. DOX and LAP have been reported to be potent ICD inducers.…”

Ferroptosis: a novel regulated cell death participating in cellular stress response, radiotherapy, and immunotherapy

“…immune response, exerting a potential antitumor tumor strategy [196,197]. LAP-Fe 2+ complexes synergistically trigger ferroptosis and ICD in tumor cells in a remotely controllable manner [198]. Biomimetic magnetosomes composed of Fe 3 O 4 magnetic nanoclusters, TGF-β inhibitors, and PD-1 antibodies can achieve synergistic cancer treatment through ferroptosis and immunomodulatory [199].…”

Protein Binding Nanoparticles as an Integrated Platform for Cancer Diagnosis and Treatment

“…[ 22 , 23 ] Moreover, polydopamine has excellent photothermal properties and can target the tumor environment with responsive to the weakly acidic condition and the high concentration of GSH. [ 24 , 25 , 26 ] Thus, polydopamine has been suggested as a potential nanoplatform for functional protein immobilization in the context of combination PTT treatment. [ 24 , 25 ] Liposome formulations have been successfully used as nanocarriers for passive and active targeted delivery.…”

“…[ 24 , 25 , 26 ] Thus, polydopamine has been suggested as a potential nanoplatform for functional protein immobilization in the context of combination PTT treatment. [ 24 , 25 ] Liposome formulations have been successfully used as nanocarriers for passive and active targeted delivery. [ 27 , 28 , 29 ] Using liposome encapsulation, nanoparticles can be selectively adsorbed in target tissues, and proteins can be protected and efficiently transported to the target site, at effective concentration.…”