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안원경Wonkyung Ahn
고려대학교 의과대학
Biomaterials, Feb 03 2025, 318 S0142-9612(25)00085-7 | https://doi.org/10.1016/j.biomaterials.2025.123166
Hierarchical protein nano-crystalline hydrogel with extracellular vesicles for ectopic lymphoid structure formation
Wonkyung Ahn a,b,1, Jihoon Han c,d,1, Nayeon Kim a, Yeong Ha Hwang c,d, Wonjun Kim a, Yeram Lee a, Dong Yun Lee e, In Woo Cheong f, Koohee Han a, Gi-Hoon Nam b, In-San Kim c,d, Eun Jung Lee a
aDepartment of Chemical Engineering, School of Chemical Engineering and Applied Chemistry, Kyungpook National University, Daegu, 41566, Republic of Korea
bDepartment of Biochemistry & Molecular Biology, Korea University College of Medicine, Seoul, 02841, Republic of Korea
cKU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02842, Republic of Korea
dChemical & Biological Integrative Research Center, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea
eDepartment of Polymer Science and Engineering, Kyungpook National University, Daegu, 41566, Republic of Korea
fDepartment of Applied Chemistry, School of Chemical Engineering and Applied Chemistry, Kyungpook National University, Daegu, 41566, Republic of Korea
1These authors contributed equally to this work.
Corresponding authors: In-San Kim, Eun Jung Lee
aDepartment of Chemical Engineering, School of Chemical Engineering and Applied Chemistry, Kyungpook National University, Daegu, 41566, Republic of Korea
bDepartment of Biochemistry & Molecular Biology, Korea University College of Medicine, Seoul, 02841, Republic of Korea
cKU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02842, Republic of Korea
dChemical & Biological Integrative Research Center, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, 02792, Republic of Korea
eDepartment of Polymer Science and Engineering, Kyungpook National University, Daegu, 41566, Republic of Korea
fDepartment of Applied Chemistry, School of Chemical Engineering and Applied Chemistry, Kyungpook National University, Daegu, 41566, Republic of Korea
1These authors contributed equally to this work.
Corresponding authors: In-San Kim, Eun Jung Lee
Abstract
Among cancer therapies, immune checkpoint blockade (ICB) has emerged as a prominent approach, substantially enhancing anti-tumor immune responses. However, the efficacy of ICB is often limited in the absence of a pre-existing immune response within the tumor microenvironment. Here, we introduce a novel hierarchical protein hydrogel platform designed to facilitate the formation of artificial tertiary lymphoid structures (aTLS), thereby improving ICB efficacy. Through the integration of self-assembling ferritin protein nanocages, rec1-resilin protein, and CP05 peptide, our hierarchical hydrogels provide a structurally supportive and functionally adaptive scaffold capable of on-demand self-repair in response to mild thermal treatments. The effective encapsulation of extracellular vesicles (EVs) via the CP05 peptide ensures the formation of aTLS with germinal center-like structures within the hierarchical hydrogel. We demonstrate that, combined with ICB therapy, EV-loaded hierarchical hydrogels also induce the TLS within the tumor, markedly promoting immune responses against ICB-resistant tumor. This bioactive hydrogel platform offers a versatile tool for enhancing a broad range of immunotherapies, with potential applications extending beyond TLS to other frameworks that support complex tissue architectures.
논문정보
- Research article
- 2025년 02월 (BRIC 등록일 2025-02-13)
- 국내 연구진
- 바이오·의료융합 > 바이오소재
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