title: Epidermal growth factor (EGF) fragment-guided anticancer theranostic particles for pH-responsive release of doxorubicin.
abstract: EGF fragment (EGFfr) and doxorubicin were chemically co-decorated on single magnetic nanoparticles (MNPs) for concomitant cancer targeting and treatment. Magnetic nanoparticles were prepared by the precipitation of ferric chloride hydrates in an ammonia solution and subsequent surface-functionalization with amines. The terminal thiol group of the EGF fragment was first conjugated to surface amines of the MNPs using a heterofunctional crosslinker, and doxorubicin was sequentially conjugated to the MNPs via a hydrazone linker, where the degree of subsitution of the surface amines to EGFfr was varied from 1% to 40%. The decorated doxorubicin showed clear pH-dependency in the release profile, and doxorubicin showed fast release at pH 5.0 in comparison to pH 7.4. The EGF-decorated MNPs were tested for differential cellular uptakes against EGF overexpressing cells (A549), and the uptake levels gradually increased to 10% and saturated, which was quantified by ICP-OES. Internalized doxorubicin was also visualized by confocal microscopy, and A549 cells with EGF-decorated MNPs with EGF decoration showed higher fluorescence intensity of doxorubicin than those with non-decorated MNPs. Anti-cancer activity of the MNPs was compared at various concentrations of doxorubicin and EGFfr. Decoration of EGFfr significantly increased the anti-cancer activity of doxorubicin-incorporated MNPs in A549 cells; however, EGFfr alone did not affect the viability of the cells. Thus, we concluded that MNPs with optimized EGFfr and doxorubicin ratios showed higher targeting and drug payload against EGF receptor overexpressing cancer cells.
authors.affiliation: Department of Medical Biomaterials Engineering, Kangwon National University, Chuncheon, 24341, Republic of Korea.
authors.forename: Myun Koo
authors.initials: MK
authors.lastname: Kang
authors.affiliation: Department of Medical Biomaterials Engineering, Kangwon National University, Chuncheon, 24341, Republic of Korea.
authors.forename: Wei
authors.initials: W
authors.lastname: Mao
authors.affiliation: Innovation Lab., Cosmax R&I Center, Seongnam-si, Republic of Korea.
authors.forename: Jun Bae
authors.initials: JB
authors.lastname: Lee
authors.affiliation: Department of Medical Biomaterials Engineering, Kangwon National University, Chuncheon, 24341, Republic of Korea; Institute of Bioscience and Biotechnology, Kangwon National University, Republic of Korea. Electronic address: hsyoo@kangwon.ac.kr.
authors.forename: Hyuk Sang
authors.initials: HS
authors.lastname: Yoo
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002712:Chlorides / Q000737:chemistry; D004317:Doxorubicin / Q000737:chemistry* / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D004815:Epidermal Growth Factor / Q000737:chemistry* / Q000494:pharmacology*; D005290:Ferric Compounds / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D058185:Magnetite Nanoparticles / Q000737:chemistry; D000068936:Theranostic Nanomedicine / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D002712:Chlorides; D004337:Drug Carriers; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; D004815:Epidermal Growth Factor; D004317:Doxorubicin; C024555:ferric chloride
keywords: Anticancer; Doxoruicin; Epidermal growth factor; Nanoparticle; pH-responsive