Abstract
Breast cancer (BC), the most common cancer in women, is closely related to ferroptosis, which is an iron-dependent form of cell death. Gambogic acid (GA), the main active ingredient extracted from the dry resin secreted by Garcinia cambogia, can effectively induce ferroptosis in tumor cells. However, its application is limited by poor water solubility, short half-life, and vascular irritation. Moreover, the sensitivity of cells to ferroptosis is positively correlated with the concentration of intracellular iron ions, which based on transferrin (Tf)-Tf receptor (TfR) pathway. Increasing intracellular iron ions within tumor cells may enhance GA-induced ferroptosis. Based on the high expression of TfR in tumor cells, Tf can be both a tumor-target modification and an Fe3+ carrier. Therefore, GA-loaded Tf-modified liposomes (GA@Tf-Lip) with pH-responsive properties were developed. GA@Tf-Lip increased the intracellular iron ion content of MCF-7 cells, promoted the Fenton reaction to increase the level of ROS, downregulated the GSH content, and accelerated lipid peroxide accumulation. The distribution of the formulation by in vivo imaging experiments showed that the prepared GA@Tf-Lip had a higher drug accumulation at tumor sites and exhibited a good antitumor effect by promoting ferroptosis. Overall, GA@Tf-Lip exerted a good anti-BC effect, which is expected to provide a new strategy for the treatment of BC and the clinical transformation of GA.
Data availability
The data supporting the findings of this study are available from the corresponding author upon reasonable request.
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Acknowledgements
This work was financially supported by Programs of the National Natural Science Foundation of China (grant number 82274066); National Key Research and Development Program of China (grant 2022YFC3501705); Shanghai Leading Talent (grant number 2019100); Program of Shanghai Academic/Technology Research Leader (grant 22XD1423000); “Shuguang Program” supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission (grant number 20SG43); Project from Shanghai Committee of Science and Technology (grant number 22S21901200 and 21010504200); Youth Talent Program from the Shanghai Municipal Health Commission (Grant 2022YQ030); Natural Science Foundation of Shanghai (grant number 21ZR1460800 and 22ZR1459000); Excellent Young medical talents Training Program of Pudong New Area Health Commission (grant number PWRq2024-42); National Traditional Chinese Medicine Inheritance and Innovation Development Pilot Zone Construction Project in Pudong New Area (grant number PDZY-2025-0722); Scientific Research Fund of Wu Jie-ping Medical Foundation (grant number 320.6750.2023-19-53).
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Wenqing Rong: Writing—original draft, Writing—review and editing, Formal Analysis, Data Curation, Investigation. Minquan Zhang: Writing—original draft, Writing—review and editing, Formal Analysis, Data Curation, Investigation. Siqi Yang: Writing—original draft, Writing-review and editing, Formal Analysis, Data Curation, Investigation. Kaiwen Wang: Writing—review and editing, Conceptualization, Investigation, Formal analysis. Xiaoping Yang: Writing—review and editing, Investigation, Formal analysis. Guolei Zhang: Writing—review and editing, Visualization, Investigation. Zhe Li: Writing—review and editing, Conceptualization, Methodology, Visualization. Yue Ding: Writing—review and editing, Resources, Funding acquisition, Methodology. Tong Zhang: Writing—review and editing, Project administration, Supervision, Resources, Methodology, Funding acquisition, Conceptualization. Yun Gai: Writing—review and editing, Project administration, Supervision, Resources, Methodology, Funding acquisition, Conceptualization. Jinshuai Lan: Writing—review and editing, Supervision, Funding acquisition, Resources, Project administration, Methodology, Conceptualization.
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All animal experimental protocols were approved by the Institutional Animal Care and Use Committee of Shanghai University of Traditional Chinese Medicine (PZSHUTCM2309080007, PZSHUTCM2309110010). All experiments were performed in accordance with the Guidelines for the Care and Use of Laboratory Animals of Shanghai University of Traditional Chinese Medicine. At the end of the experiments, the mice were euthanized by intraperitoneal injection of excessive 1.25% tribromoethanol (20 μL/g), the rabbits were euthanized via intraperitoneal injection injection of excessive soidum pentobarbital (100 mg/kg). Authors confirmed that all animal experiments were performed in accordance with ARRIVE guidelines.
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Rong, W., Zhang, M., Yang, S. et al. Gambogic acid-loaded transferrin-modified liposomes enhancing potent ferroptosis in breast cancer. Sci Rep (2026). https://doi.org/10.1038/s41598-026-47971-z
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DOI: https://doi.org/10.1038/s41598-026-47971-z
