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강원대학교 약학대학

Adv. Funct. Mater., 12 June 2025 | https://doi.org/10.1002/adfm.202420430 Self-Cascade Catalytic Reaction–Assisted Apoptosis/Calcicoptosis/Ferroptosis Induction with Microsphere-Aggregated Hydrogels in Triple-Negative Breast Cancer Therapy

ChaeRim Hwang¹, Yeoung Eun Choi¹, Song Yi Lee², Mrinmoy Karmakar¹, Qiaojun Hao¹, Junmin Lee³, and Hyun-Jong Cho^1*

¹Department of Pharmacy, College of Pharmacy, Kangwon National University, Chuncheon, 24341 Republic of Korea
²Kangwon Institute of Inclusive Technology, Kangwon National University, Chuncheon, 24341 Republic of Korea
³Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), Pohang, 37673 Republic of Korea

C.H. and Y.E.C. contributed equally to this work.
Corresponding Author : Hyun-Jong Cho

Abstract

Cisplatin-loaded hyaluronic acid-dopamine microsphere (MS) is interconnected by metal ion (e.g., calcium ion and iron ion)-catechol coordination and polydopamine linkages to form an MS-aggregated hydrogel (MAH) system to enable convenient peritumoral injection and efficient tumor infiltration in triple-negative breast cancer (TNBC) therapy. Cisplatin (inhibition of DNA replication and cellular H2O2 generation), calcium peroxide (self-generation of H2O2), and ferrous sulfate (conversion of H2O2 to OH radicals) are integrated into the MAH system for chemo/cascade chemodynamic therapy. Reactive oxygen species (ROS) are produced by calcium peroxide and ferrous sulfate, which can assist Ca2+ overload in inducing calcicoptosis in cancer cells. Both iron and calcium ions increase the degree of lipid peroxidation, leading to enhanced ferroptosis in cancer cells. Cisplatin and ROS generation induces apoptosis in cancer cells. Viscoelastic modulation for prolonged therapeutic delivery with enhanced tumor penetration of the jammed MAH system is demonstrated physicochemically and mechanically. Anticancer capabilities are also assessed in 4T1 cells and orthotopic 4T1 tumor mouse models. Remarkably, the MAH system strongly inhibited the recurrence of residual 4T1 tumors in a mouse model. These findings indicate that the MAH system can be applied for the ROS-assisted induction of multiple apoptosis/calcicoptosis/ferroptosis pathways in TNBC therapy.

논문정보

형식Research article
게재일2025년 06월 (BRIC 등록일 2025-06-16)
연구진국내 연구진
분야 의약학 > 약학

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