Magnetic lipid-poly(lactic-co-glycolic acid) nanoparticles conjugated with epidermal growth factor receptor antibody for dual-targeted delivery of CPT-11.

Autor: Shivanna AT; Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan; Barrow Neurological Institute, Phoenix, AZ 85013, USA., Dash BS; Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan., Lu YJ; Department of Neurosurgery, Chang Gung Memorial Hospital, Linkou, Kwei-San, Taoyuan 33305, Taiwan., Lin WT; Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan., Chen JP; Department of Chemical and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, Taiwan; Department of Neurosurgery, Chang Gung Memorial Hospital, Linkou, Kwei-San, Taoyuan 33305, Taiwan; Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 33302, Taiwan; Department of Materials Engineering, Ming Chi University of Technology, Tai-Shan, New Taipei City 24301, Taiwan. Electronic address: jpchen@mail.cgu.edu.tw.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2024 Dec 25; Vol. 667 (Pt A), pp. 124856. Date of Electronic Publication: 2024 Oct 24.
DOI: 10.1016/j.ijpharm.2024.124856
Abstrakt: To entrap sparingly water-soluble drugs like CPT-11 (irinotecan), the poly(lactic-co-glycolic acid) (PLGA) nanoparticle (NP) is highly favored due to its low cytotoxicity and approval for clinical use. On the other hand, entrapping hydrophobic oleic acid-coated iron oxide magnetic nanoparticles (OMNP) in PLGA NP can provide a nanovehicle for magnetically targeted drug delivery. Our goal in this study is to develop a new dual-targeted magnetic lipid-polymer NP for the delivery of CPT-11. We first co-entrap OMNP and CPT-11 in self-assembled lipid-PLGA NP to prepare OLNP@CPT-11. The OLNP@CPT-11 surface was modified with an epidermal growth factor receptor (EGFR) antibody Cetuximab (CET), which can actively target the overexpressed EGFR on the U87 glioblastoma cell surface. The OLNP-CET@CPT-11 enables dual targeting through both external magnetic guidance and CET-mediated active targeting. The NP was characterized for physicochemical properties using various analytical techniques. In vitro study confirms ligand-receptor interaction results in enhanced endocytosis of OLNP-CET@CPT-11 by U87 cells, which offers increased cytotoxicity and elevated cell apoptosis rates. Furthermore, magnetic guidance of OLNP-CET@CPT-11 to U87 cells can induce cell death exclusively in the magnetically targeted zone. The dual-targeted strategy also provides the best therapeutic efficacy against subcutaneously implanted U87 tumors in nude mice with intravenously delivered OLNP-CET@CPT-11.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Jyh-Ping Chen reports financial support was provided by Chang Gung Memorial Hospital Linkou. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper].
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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