Gastrointestinally absorbable lactoferrin-heparin conjugate with anti-angiogenic activity for treatment of brain tumor
- Authors
- Hwang, Hae Hyun; Kim, Hyung Shik; Lee, Dong Yun
- Issue Date
- Mar-2023
- Publisher
- Elsevier B.V.
- Keywords
- Heparin; Lactoferrin; Brain cancer; Oral delivery; Angiogenesis
- Citation
- Journal of Controlled Release, v.355, pp.730 - 744
- Indexed
- SCIE
SCOPUS
- Journal Title
- Journal of Controlled Release
- Volume
- 355
- Start Page
- 730
- End Page
- 744
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/191602
- DOI
- 10.1016/j.jconrel.2023.02.002
- ISSN
- 0168-3659
- 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.
- Files in This Item
-
Go to Link
- Appears in
Collections - 서울 공과대학 > 서울 생명공학과 > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/191602)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.