Dual-targeting immunoliposomes using angiopep-2 and CD133 antibody for glioblastoma stem cells
- Authors
- Kim, Jung Seok; Shin, Dae Hwan; Kim, Jin-Seok
- Issue Date
- Jan-2018
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- Glioblastoma stem cell; Angiopep-2; Anti-CD133 monoclonal antibody; Blood-brain barrier; Liposome; Dual targeting
- Citation
- JOURNAL OF CONTROLLED RELEASE, v.269, pp 245 - 257
- Pages
- 13
- Journal Title
- JOURNAL OF CONTROLLED RELEASE
- Volume
- 269
- Start Page
- 245
- End Page
- 257
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/4770
- DOI
- 10.1016/j.jconrel.2017.11.026
- ISSN
- 0168-3659
1873-4995
- Abstract
- Glioblastoma stem cells (GSCs), which are identified as subpopulation of CD133(+)/ALDH1(+), are known to show resistance to the most of chemotherapy and radiation therapy, leading to the recurrence of tumor in glioblastoma multiforme (GBM) patients. Also, delivery of temozolomide (TMZ), a mainline treatment of GBM, to the GBM site is hampered by various barriers including the blood-brain barrier (BBB). A dual-targeting immunoliposome encapsulating TMZ (Dual-LP-TMZ) was developed by using angiopep-2 (An2) and anti-CD133 monoclonal antibody (CD133 mAb) for BBB transcytosis and specific delivery to GSCs, respectively. The size, zeta potential and drug encapsulation efficiency of Dual-LP-TMZ were 203.4 nm in diameter, - 1.6 mV and 99.2%, respectively. The in vitro cytotoxicity of Dual-LP-TMZ against U87MG GSCs was increased by 425- and 181-folds when compared with that of free TMZ and non-targeted TMZ liposome (LP-TMZ) (10.3 mu M vs. 4380 mu M and 1869 mu M in IC50, respectively). Apoptosis and anti-migration ability of Dual-LP-TMZ in U87MG GSCs were also significantly enhanced comparing with those of free TMZ or LP-TMZ. In vivo study clearly showed a significant reduction in tumor size after intravenous administrations of Dual-LP-TMZ to the orthotopically-implanted brain tumor mice when compared with free TMZ or LP-TMZ. Increased life span (ILS) and median survival time (MST) of tumor-bearing mice were also increased when treated with Dual-LP-TMZ (211.2% in ILS and 49.2 days in MST) than with free TMZ (0% in ILS and 23.3 day in MST). These data indicate that conjugation of both An2 peptide and CD133 mAb to TMZ-encapsulating liposome is very effective in delivering the TMZ to GSCs via BBB, suggesting a potential use of Dual-LP-TMZ as a therapeutic modality for GBM.
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