김효철 (서울대학교 의과대학, 서울대학교병원)

한빛사논문

조회94

서울대학교 의과대학, 서울대학교병원

CV File 184 kb

Small, Aug 07 2024, | https://doi.org/10.1002/smll.202400287 Intravascular Casting Radiopaque Hydrogel Systems for Transarterial Chemo/Cascade Catalytic/Embolization Therapy of Hepatocellular Carcinoma

Song Yi Lee ^1,2, Jin Woo Choi ³, ChaeRim Hwang ¹, JiHye Park¹, Mrinmoy Karmakar ¹, Ji Won Huh ¹, Dae-Duk Kim ⁴, Hyo-Cheol Kim ³, Hyun-Jong Cho¹

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 Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.

⁴College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea.

S.Y.L. and J.W.C. contributed equally to this work.

Corresponding Authors: Hyo-Cheol Kim, Hyun-Jong Cho

Abstract

This paper introduces catheter-directed intravascular casting hydrogels for transarterial chemo/starvation/chemodynamic embolization (TACSCE) therapy of hepatocellular carcinoma (HCC). Comprising Mn ion-crosslinked hyaluronic acid-dopamine (HD) with glucose oxidase (for glucose decomposition to H₂O₂ in starvation therapy), doxorubicin (for chemotherapy), and iopamidol (for X-ray imaging), these hydrogels are fabricated for transarterial embolization therapy guided by X-ray fluoroscopy. Mn⁴⁺ (from MnO₂) demonstrates strong coordination with the catechol group of HD, providing hypoxia relief through O₂ generation and cellular glutathione (GSH) consumption, compared to the OH radical generation potential of Mn²⁺. The gelation time-controlled, catheter-injectable, and rheologically tuned multitherapeutic/embolic gel system effectively reaches distal arterioles, ensuring complete intravascular casting with fewer complications related to organic solvents. Glucose deprivation, cascade reactive oxygen species (ROS) generation, GSH depletion, and sustained release profiles of multiple drug cargos from the hydrogel system are also achieved. The combined chemo/starvation/chemodynamic efficacies of these designed hydrogel systems are confirmed in HCC cell cultures and HCC-bearing animal models. The developed radiopaque/injectable/embolic/sol-to-gel transformable systems for TACSCE therapy may offer enhanced therapeutic efficacies compared to typical transarterial embolization and transarterial chemoembolization procedures for HCC.

논문정보

형식Research article
게재일2024년 08월 (BRIC 등록일 2024-08-08)
연구진국내 연구진
분야 의약학 > 약학

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