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조회102

건국대학교

Nano Today, Available online 21 February 202 | https://doi.org/10.1016/j.nantod.2025.102677 Lenalidomide-utilizing self-assembled immunogenic cell death-inducing heparin/doxorubicin nanocomplex for anticancer immunotherapy

Minho Seo ^a,1, Yun-Hwa Jeong ^b,1, Bison Seo ^a,c,1, Sung-Kyun Han^d, Seong-Bin Yang ^a, Jun-Hyuck Lee ^a, Jae-Hyeon Lee ^a, Gaeun Ma^a, Eun-Seok Park ^d, Jeong Uk Choi^b,e, Jooho Park ^a,c

^aBK21 Program, Department of Applied Life Science, Konkuk University, Chungju 27478, Republic of Korea
^bDepartment of Regulatory Science, Graduate School, Kyung Hee University, Seoul 02453, Republic of Korea
^cCollege of Biomedical and Health Science, Konkuk University, Chungju 27478, Republic of Korea
^dSchool of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 16419, Republic of Korea
^eCollege of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea

¹These authors contributed equally to this work.
Corresponding authors: Jeong Uk Choi, Jooho Park

Abstract

Lenalidomide (LEN), a thalidomide analogue widely used in the treatment of multiple myeloma, has had limited application in other cancer therapies due to challenges such as its immune-based cytotoxic limitations, low efficacy in solid tumors, and the risk of thrombosis. To overcome these hurdles, we developed a novel self-assembling immunogenic nanocomplex that combines lenalidomide with unfractionated heparin (UFH), a highly negatively charged anticoagulant, and doxorubicin (DOX), a potent cytotoxic agent. The nanocomplex is formed through charge-charge and hydrophobic interactions, resulting in a self-assembled UFH/DOX/LEN complex (HepDL) that generates nanoparticles approximately 140 nm in size in saline. Molecular dynamics (MD) simulations confirmed the formation process of the HepDL nanocomplex. These carrier-free, drug-only nanoparticles induce immunogenic cell death (ICD) by releasing DOX in a controlled manner, thereby activating CD8+ T cells, natural killer (NK) cells, natural killer T (NKT) cells, and dendritic cells (DCs). This leads to enhanced anti-tumor efficacy in the CT26.CL25 tumor model, demonstrating a robust immune-boosting effect. This study presents a significant advancement in the development of immunogenic nanoparticles incorporating lenalidomide for cancer treatment.

논문정보

형식Research article
게재일2025년 02월 (BRIC 등록일 2025-02-27)
연구진국내 연구진
분야 의약학 > 약학

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