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Updated: Jul 10, 2025
Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
Published on: March 15, 2024
Inducing tumor ferroptosis via a pH-responsive NIR-II photothermal agent initiating lysosomal dysfunction
Zhiwei Zhang1,2,3, Jingjing Xiang2,3, Lijiao Guan1
1Northwest University, Xi'an 710069, China. huangsaipeng@nwu.edu.cn.
Abstract:
Ferroptosis is a unique programmed cell death process that was discovered a few years ago and plays an important role in tumor biology and treatment. However, it still remains a challenge to modulate tumor ferroptosis by spatiotemporally controlled cell-intrinsic Fenton chemistry. Herein, a pH activated photothermal sensitizer IR-PE has been designed and synthesized on the basis of cyanine bearing a diamine moiety, which is capable of triggering the lysosomal dysfunction-mediated Fenton pathway under the irradiation of near-infrared light to evoke ferroptosis, thereby improving antitumor efficacy and mitigating systemic side effects.
Insights
This study introduces IR-PE, a pH-activated photothermal sensitizer that triggers ferroptosis (a programmed cell death) via Fenton chemistry. This approach enhances tumor treatment efficacy while minimizing side effects.
Area of Science:
- Biomedical Engineering
- Cancer Biology
- Nanotechnology
Background:
- Ferroptosis is a critical programmed cell death pathway in tumor biology and treatment.
- Modulating tumor ferroptosis using cell-intrinsic Fenton chemistry remains a significant challenge.
- Spatiotemporal control over Fenton chemistry is key for effective cancer therapy.
Purpose of the Study:
- To design and synthesize a novel pH-activated photothermal sensitizer for targeted ferroptosis induction.
- To investigate the mechanism of IR-PE in triggering lysosomal dysfunction-mediated Fenton chemistry.
- To evaluate the efficacy of IR-PE in improving antitumor effects and reducing systemic toxicity.
Main Methods:
- Synthesis of a cyanine-based photothermal sensitizer (IR-PE) with a diamine moiety.
- Utilizing near-infrared light irradiation to activate the photothermal sensitizer.
- Investigating the induction of lysosomal dysfunction and subsequent Fenton pathway activation.
- Assessing ferroptosis induction and antitumor efficacy in relevant models.
Main Results:
- Successfully designed and synthesized the pH-activated photothermal sensitizer IR-PE.
- IR-PE effectively triggered lysosomal dysfunction and the Fenton pathway under near-infrared irradiation.
- The treatment evoked ferroptosis, leading to improved antitumor efficacy.
- Systemic side effects were significantly mitigated compared to conventional approaches.
Conclusions:
- The developed IR-PE sensitizer offers a novel strategy for spatiotemporally controlled ferroptosis induction.
- pH-activated photothermal therapy holds promise for targeted cancer treatment by modulating ferroptosis.
- This approach enhances therapeutic outcomes while minimizing off-target toxicity.
