title: Co-delivery of paclitaxel and gemcitabine via CD44-targeting nanocarriers as a prodrug with synergistic antitumor activity against human biliary cancer.
abstract: Multi-drug delivery focuses on different signaling pathways in cancer cells that have synergistic anti-proliferative effects. In this study, we developed multi-prodrug nanocarriers (MPDNCs) consisting of poly (l-lysine)-carboxylate PTX (PLL-PTX) and hyaluronic acid-conjugated GEM (HA-GEM) for CD44-targeted synergistic biliary cancer therapy. An in vitro study of cell viability and mRNA expression levels and an in vivo study showed that MPDNCs more effectively inhibit proliferation in CD44-overexpressing cancer cells (HuCCT1) than in cells with lower CD44 expression (SCK) by synergistically inducing apoptosis. Consequently, these results demonstrate that MPDNCs are prodrugs with synergistic cancer therapeutic efficacy and effective cellular uptake at target cells compared to free drugs, indicating their strong potential as efficient multi-drug-carrying nano-platforms for cancer treatment.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 120-749, South Korea; Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, South Korea.
authors.forename: Ilkoo
authors.initials: I
authors.lastname: Noh
authors.affiliation: Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 120-749, South Korea.
authors.forename: Hyun-Ouk
authors.initials: HO
authors.lastname: Kim
authors.affiliation: Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 120-749, South Korea; Department of Chemistry, Stanford University, Stanford, CA 94305-5080, USA.
authors.forename: Jihye
authors.initials: J
authors.lastname: Choi
authors.affiliation: Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul 120-752, South Korea.
authors.forename: Yuna
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 135-720, South Korea.
authors.forename: Dong Ki
authors.initials: DK
authors.lastname: Lee
authors.affiliation: Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul 120-752, South Korea. Electronic address: ymhuh@yuhs.ac.
authors.forename: Yong-Min
authors.initials: YM
authors.lastname: Huh
authors.affiliation: Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 120-749, South Korea. Electronic address: haam@yonsei.ac.kr.
authors.forename: Seungjoo
authors.initials: S
authors.lastname: Haam
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004337:Drug Carriers; D006801:Humans; D018960:Hyaluronan Receptors / Q000187:drug effects*; D053758:Nanoparticles; D017239:Paclitaxel / Q000008:administration & dosage; D000093542:Gemcitabine
chemical_list: C497483:CD44 protein, human; D004337:Drug Carriers; D018960:Hyaluronan Receptors; D003841:Deoxycytidine; D017239:Paclitaxel; D000093542:Gemcitabine
keywords: Biliary cancer; CD44 targeting; Combined cancer therapy; Gemcitabine; Paclitaxel; Polymeric prodrug