한빛사논문
- 조회489
Hae Hyun Hwang a,1, Hyung Shik Kim a,1, Dong Yun Lee a,b,c
aDepartment of Bioengineering, College of Engineering, BK FOUR Biopharmaceutical Innovation Leader for Education and Research Group, Hanyang University, Seoul 04763, Republic of Korea
bInstitute of Nano Science and Technology (INST), Institute for Bioengineering and Biopharmaceutical Research (IBBR), Hanyang University, Seoul 04763, Republic of Korea
cElixir Pharmatech Inc., Seoul 07463, Republic of Korea
1These authors contributed equally (co-first authors).
Corresponding author : Dong Yun Lee
Abstract
Glioblastoma multiforme (GBM) is a central nervous system disease with poor prognosis. Curative treatments for GBM involve chemotherapy, radiotherapy, and surgical pathways. Recently, antiangiogenic therapy through medications has been tried to slow tumor growth, but the drugs can induce side effects. To overcome these limitations, we developed a new orally absorbable form of heparin that can attenuate angiogenic activity by binding to growth factors around the tumor tissue. We conjugated lactoferrin (Lf) to heparin because Lf can be orally absorbed, and it interacts with the lactoferrin receptor (Lf-R) expressed on the intestine, blood-brain barrier (BBB), and glioma tumor masses. We successfully conjugated Lf and heparin by amide bond formation, as evidenced by advanced physicochemical properties such as pharmacokinetics and stability in acidic condition. This new material inhibited angiogenesis in vitro without toxicity. In addition, Lf-heparin administered orally to GBM orthotopic mice was absorbed in the small intestine and delivered specifically to the brain tumor by receptor transcytosis (Lf-R). Lf-heparin further attenuated angiogenesis progression in GBM orthotopic mice. Based on these results, Lf-heparin shows potential as a new oral medication for treatment of glioblastoma.
논문정보
- Research article
- 2023년 03월 (BRIC 등록일 2023-02-24)
- 국내 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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