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Ayeskanta MohantyAyeskanta Mohanty
전남대학교
Adv. Healthc. Mater., Mar 20 2025, | https://doi.org/10.1002/adhm.202500272
Programable Prodrug Nanomodulator Targets Tumor Redox Homeostasis Imbalance to Amplify Disulfidptosis and Immunogenic Pyroptosis for Breast Tumor Immunotherapy
Ayeskanta Mohanty 1, Adityanarayan Mohapatra 1,2, Woojin Yang 3, Seunghyun Choi 3, Aravindkumar Sundaram 1,2, Yong-Yeon Jeong 2,4, Chang-Moon Lee 5,6, Jiwon Seo 3, In-Kyu Park 1,2
1Department of Biomedical Sciences and BioMedical Sciences Graduate Program (BMSGP), Chonnam National University Medical School, Gwangju, 61469, Republic of Korea.
2DR Cure Inc., Hwasun, 58128, Republic of Korea.
3Department of Chemistry, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea.
4Department of Radiology, Chonnam National University Medical School and Hwasun Hospital, 322 Seoyang-Ro, Hwasun-Gun, Jeollanam-do, 58128, Republic of Korea.
5School of Healthcare and Biomedical Engineering, Chonnam National University, Yeosu, 59626, Republic of Korea.
6Leading Research Center of Total Solution for Osteoporosis Treatment, Chonnam National University, Yeosu, 59626, Republic of Korea.
Corresponding Authors: Chang-Moon Lee, Jiwon Seo, In-Kyu Park
1Department of Biomedical Sciences and BioMedical Sciences Graduate Program (BMSGP), Chonnam National University Medical School, Gwangju, 61469, Republic of Korea.
2DR Cure Inc., Hwasun, 58128, Republic of Korea.
3Department of Chemistry, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea.
4Department of Radiology, Chonnam National University Medical School and Hwasun Hospital, 322 Seoyang-Ro, Hwasun-Gun, Jeollanam-do, 58128, Republic of Korea.
5School of Healthcare and Biomedical Engineering, Chonnam National University, Yeosu, 59626, Republic of Korea.
6Leading Research Center of Total Solution for Osteoporosis Treatment, Chonnam National University, Yeosu, 59626, Republic of Korea.
Corresponding Authors: Chang-Moon Lee, Jiwon Seo, In-Kyu Park
Abstract
Despite the great potential of photodynamic therapy (PDT), its success remains compromised by the abnormal redox homeostasis of tumor cells, which supports survival, growth, and resistance to oxidative therapeutic interventions by neutralizing reactive oxygen species (ROS). To overcome this barrier, a multifunctional prodrug nanomodulator (Pro@FLNC) is designed to induce disulfidptosis and immunogenic pyroptosis to trigger an antitumor immune response. Pro@FLNC features a prodrug core-shell structure where ursolic acid (UA) and Chlorin e6 (Ce6) are conjugated via a GSH-responsive linker and encapsulated in a DSPE-PEG-FA lipid shell for enhanced stability, biocompatibility, and tumor-specific targeting. Within the tumor microenvironment (TME), Pro@FLNC depletes intracellular GSH, disrupts redox homeostasis, and releases Ce6 and UA, triggering oxidative stress and mitochondrial dysfunction. These mechanisms amplify ROS production, promote lipid peroxidation, and initiate disulfidptosis, evidenced by increased SLC7A11 expression and F-actin collapse. Elevated ROS levels and metabolic imbalance-triggered disulfidptosis further activate immunogenic pyroptosis, releasing damage-associated molecular patterns (DAMPs) that stimulate dendritic cell maturation and cytotoxic T-cell activation. Together, Pro@FLNC reshapes the TME, reduces immunosuppressive cells, and promotes CD8+ T-cell infiltration, effectively suppressing primary tumors and metastases. This programmed prodrug nanomodulator offers a promising strategy to enhance PDT and immunotherapy for advanced breast cancer.
논문정보
- Research article
- 2025년 03월 (BRIC 등록일 2025-03-24)
- 국내 연구진
- 바이오·의료융합 > 바이오소재
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