Multifunctional porphyrinic metal-organic framework-based nanoplatform regulating reactive oxygen species achieves efficient imaging-guided cascaded nanocatalytic therapy

Haoyu Chen; Minjuan Wang; Qiquan Yang; Jing Liu; Feng Liu; Xiaohua Zhu; Shu Huang; Peng Yin; Xingfeng Wang; Haitao Li; Youyu Zhang; Meiling Liu; Mingjie Wei; Shouzhuo Yao; Yang Liu

doi:10.1016/j.jcis.2025.01.041

Multifunctional porphyrinic metal-organic framework-based nanoplatform regulating reactive oxygen species achieves efficient imaging-guided cascaded nanocatalytic therapy

J Colloid Interface Sci. 2025 Jan 8;684(Pt 1):423-438. doi: 10.1016/j.jcis.2025.01.041. Online ahead of print.

Authors

Haoyu Chen¹, Minjuan Wang², Qiquan Yang³, Jing Liu³, Feng Liu³, Xiaohua Zhu³, Shu Huang³, Peng Yin³, Xingfeng Wang², Haitao Li³, Youyu Zhang³, Meiling Liu⁴, Mingjie Wei⁵, Shouzhuo Yao³, Yang Liu⁶

Affiliations

¹ Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research (Ministry of Education, China), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha 410081, China; Department of Chemistry, Kay Lab of Bioorganic Phosphorus Chemistry and Chemical Biology of Ministry of Education, Beijing Key Laboratory for Analytical Methods and Instrumentation, Tsinghua University, 100084 Beijing, China.
² School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China.
³ Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research (Ministry of Education, China), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha 410081, China.
⁴ Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research (Ministry of Education, China), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha 410081, China. Electronic address: liumeilingww@126.com.
⁵ School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China. Electronic address: weimj5@mail3.sysu.edu.cn.
⁶ Department of Chemistry, Kay Lab of Bioorganic Phosphorus Chemistry and Chemical Biology of Ministry of Education, Beijing Key Laboratory for Analytical Methods and Instrumentation, Tsinghua University, 100084 Beijing, China. Electronic address: liu-yang@mail.tsinghua.edu.cn.

PMID: 39799625
DOI: 10.1016/j.jcis.2025.01.041

Abstract

The integration of reactive oxygen species (ROS) related photodynamic therapy (PDT) with the strategy of reshaping the tumor microenvironment (TME) has emerged as a potential approach for nanodiagnostic and therapeutic interventions. However, the therapeutic efficacy based on ROS treatments may be hindered by intracellular antioxidants such as glutathione (GSH) and tumor hypoxia. To address these challenges, a nanoplatform based on GSH-responsive multifunctional porphyrinic metal-organic framework (PCN-224@Au@MnO₂@HA, PAMH) was proposed. It was developed through a layer-by-layer in-situ growth method. This method avoids the need for high-temperature calcination and complex modification processes while improving the stability of PCN-224 in a phosphate-rich environment. GSH depletion leads to oxidation-reduction imbalance in TME. With the inactivation of GSH peroxidase 4 (GPX4), the content of hydrogen peroxide (H₂O₂) increases, ultimately triggering lipid peroxidation (LPO) and promoting ferroptosis. The catalase-like activity of Au nanozymes facilitates the generation of oxygen (O₂), thereby mitigating tumor hypoxia and downregulating hypoxia-inducing factors (HIF-1α). Due to the presence of porphyrin ligands in PCN-224, the generated O₂ can be further converted to toxic singlet oxygen (¹O₂) under laser irradiation. Additionally, the platform allows near-infrared (NIR) fluorescence imaging, providing real-time information on intracellular GSH changes during PDT and ferroptosis. The PAMH nanoplatform has shown effective inhibition of tumor growth in subcutaneous models via both intravenous and intratumoral injection, indicating its potential in modulating reactive oxygen/sulfur species and reshaping TME, thereby facilitating imaging-guided cascaded nanocatalytic therapy.

Keywords: Ferroptosis; GSH consumption; Photodynamic therapy; Porphyrinic metal-organic frameworks; ROS regulation.