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Ferrocene-integrated hypericin self-assembly nanocomplex directs ferroptosis for enhanced cascade tumor photodynamic therapy and immune effects
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DOI：10.1016/j.cclet.2025.111645.png)
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Abstract
En 中文
The antioxidant and immune-suppressive microenvironment of tumors has severely limited the efficacy of photodynamic therapy (PDT). To overcome these limitations, we proposed a novel nanoparticle (PEG-PFc/Hyp) that combined hypericin (Hyp) and ferrocene for synergistic anti-tumor therapy within a single system. Briefly, the optimum PEG114 -PLL10 was reacted with ferrocene by the carboxylic acid N -succinimidyl ester(ferrocene-NHS), and the subsequent Hyp encapsulated in the above fabricated amphiphilic polymer. When under light irradiation, Hyp generated abundant reactive oxygen species (ROS) that synergized with center dot OH produced by ferrocene, leading to disrupted redox balance, amplified lethal lipid peroxidation (LPO) and inducing significant ferroptosis. Furthermore, the ferrocene could greatly alleviate hypoxia via O2 production, thereby cascaded enhancing the ROS production efficiency of PDT. As a result, the cascade augmented ROS level, alongside the glutathione (GSH) depletion in tumor cells, caused effective immunogenic cell death (ICD) and potent anti-tumor response. It turned out that the PDT-ferroptosis-ICD strategy enabled significant oxidative damage and tumor cell immunogenicity, offering great potential in cancer immunotherapy. (c) 2026 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.
Keywords:
Fenton reaction
Hypericin
Photodynamic therapy
Ferroptosis
Immunogenic cell death
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8.9
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1.2W
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3.8W
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