title: RGD-peptide conjugated inulin-ibuprofen nanoparticles for targeted delivery of Epirubicin.
abstract: Recently, chemotherapy-based polymeric nanoparticles have been extensively investigated for solid tumor treatment. Tumor targeted nanoparticles demonstrated great potential for improved accumulation in the tumor tissue, superior anticancer activity and reduced side effects. Thus, inulin-ibuprofen polymer was synthesized by esterification between inulin and ibuprofen, and RGD targeted epirubicin (EPB) loaded nanoparticles were prepared by the self-assembly of inulin-ibuprofen polymer and in situ encapsulation of EPB. RGD conjugated EPB loaded nanoparticles were characterized by dynamic light scattering (DLS) and transmission electron microscope (TEM). The EPB release from the nanoparticles showed pH-dependent profile and accelerated by the decreased pH value, which would favor the effective drug delivery in vivo. Intracellular uptake analysis suggested that RGD conjugated nanoparticles could be easily internalized by the cancer cells. In vitro cytotoxicity revealed that RGD conjugated EPB loaded nanoparticles exhibited the better antitumor efficacy compared with non-conjugated nanoparticles. More importantly, RGD conjugated EPB loaded nanoparticles showed superior anticancer effects and reduced toxicity than free EPB and non-conjugated nanoparticles by in vivo antitumor activity, EPB biodistribution and histology analysis.
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, China; Hand Surgery Research Center, Department of Hand Surgery, Affiliated Hospital of Nantong University, Nantong 226001, China.
authors.forename: Luzhong
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, China.
authors.forename: Guicai
authors.initials: G
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Gao
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Medical College, Nantong University, Nantong 226001, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Ji
authors.affiliation: Medical College, Nantong University, Nantong 226001, China.
authors.forename: Ruheng
authors.initials: R
authors.lastname: Hua
authors.affiliation: Hand Surgery Research Center, Department of Hand Surgery, Affiliated Hospital of Nantong University, Nantong 226001, China. Electronic address: zhouyoulang@ntu.edu.cn.
authors.forename: Youlang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong 226001, China. Electronic address: yangym@ntu.edu.cn.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004705:Endocytosis / Q000187:drug effects; D015251:Epirubicin / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007052:Ibuprofen / Q000138:chemical synthesis / Q000737:chemistry*; D042541:Intracellular Space / Q000378:metabolism; D007444:Inulin / Q000138:chemical synthesis / Q000737:chemistry*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009842:Oligopeptides / Q000737:chemistry*; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D009842:Oligopeptides; D015251:Epirubicin; C047981:arginyl-glycyl-aspartic acid; D007444:Inulin; D007052:Ibuprofen
keywords: Drug delivery; Epirubicin; Nanoparticle; RGD; Target