title: MT1-MMP Responsive Doxorubicin Conjugated Poly(lactic-co-glycolic Acid)/Poly(styrene-alt-maleic Anhydride) Core/Shell Microparticles for Intrahepatic Arterial Chemotherapy of Hepatic Cancer.
abstract: In this study, we demonstrated that the MT1-MMP-responsive peptide (sequence: GPLPLRSWGLK) and doxorubicin-conjugated poly(lactic-co-glycolic acid/poly(styrene-alt-maleic anhydride) core/shell microparticles (PLGA/pSMA MPs) can be applied for intrahepatic arterial injection for hepatocellular carcinoma (HCC). PLGA/pSMA MPs were prepared with a capillary-focused microfluidic device. The particle size, observed by scanning electron microscopy (SEM), was around 22 ± 3 μm. MT1-MMP-responsive peptide and doxorubicin (DOX) were chemically conjugated with pSMA segments on the shell of MPs to form a PLGA/pSMA-peptide-DOX complex, resulting in high encapsulation efficiency (91.1%) and loading content (2.9%). DOX was released from PLGA/pSMA-peptide-DOX MPs in a pH-dependent manner (∼25% at pH 5.4 and ∼8% at pH 7.4) and accumulated significantly in an MT1-MMP-overexpressing Hep3B cell line. An in vivo intrahepatic injection study showed localization of MPs on the hepatic vessels and hepatic lobes up to 24 h after the injection without any shunting to the lung. Moreover, MPs efficiently inhibited tumor growth of Hep3B hepatic tumor xenografted mouse models. We expect that PLGA/pSMA-peptide-DOX MPs can be utilized as an effective intrahepatic drug delivery system for the treatment of HCC.
authors.affiliation: Department of New Drug Development, School of Medicine, Inha University , B-308, Chungsuk Bldg, 366, Seohae-Daero, Jung-Gu, Incheon 22332, Republic of Korea.
authors.forename: Enkhzaya
authors.initials: E
authors.lastname: Davaa
authors.affiliation: Department of New Drug Development, School of Medicine, Inha University , B-308, Chungsuk Bldg, 366, Seohae-Daero, Jung-Gu, Incheon 22332, Republic of Korea.
authors.forename: Junghan
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Materials Science and Engineering, School of Molecular Science and Engineering, Vidyasirimedhi Institute of Science and Technology (VISTEC) , Rayong 21210, Thailand.
authors.forename: Ratchapol
authors.initials: R
authors.lastname: Jenjob
authors.affiliation: Department of New Drug Development, School of Medicine, Inha University , B-308, Chungsuk Bldg, 366, Seohae-Daero, Jung-Gu, Incheon 22332, Republic of Korea.
authors.forename: Su-Geun
authors.initials: SG
authors.lastname: Yang
mesh_terms: D000818:Animals; D004317:Doxorubicin / Q000737:chemistry; D006018:Glycols; D019344:Lactic Acid / Q000737:chemistry; D008113:Liver Neoplasms; D008299:Maleic Anhydrides; D053511:Matrix Metalloproteinase 14; D011100:Polyglycolic Acid / Q000737:chemistry
chemical_list: D006018:Glycols; D008299:Maleic Anhydrides; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004317:Doxorubicin; D053511:Matrix Metalloproteinase 14
keywords: doxorubicin; hepatoma; microparticle; poly(d,l-lactide-co-glycolide); poly(styrene-alt-maleic anhydride)