title: Low molecular weight heparin mediating targeting of lymph node metastasis based on nanoliposome and enzyme-substrate interaction.
abstract: The aim of our study is to develop a new function of low molecular weight heparin (LMWHEP) for targeting tumor metastatic lymph node based on LMWHEP-modified nanoliposome and LMWHEP-heparanase (HPA) interaction (LMWHEP-HPA). At First, LMWHEP-modified nanoliposomes (LMWHEP-LPs) were prepared by the electrostatic attraction and the physiochemical properties were evaluated. Then the effects of LMWHEP-HPA on the stability and drug release were investigated. In addition, the cellular uptake of LMWHEP-LPs was studied by using Hela, MCF-7, L929 and RAW264.7 cells. Finally, the targeting ability as well as the tissue distribution was examined in the mice model bearing Hela tumor lymph node metastasis. LMWHEP-LPs prepared had suitable physicochemical properties. The effect results of LMWHEP-HPA showed that LMWHEP coated on the surface of nanoliposome could be degraded by HPA. Compared with the unmodified-nanoliposome, the LMWHEP modification could improve the cellular uptake and increase the targeting ability to the metastatic lymph nodes according to LMWHEP-HPA. This study demonstrates LMWHEP is a highly promising polymer material for the targeting of tumor lymph node metastasis.
authors: School of Pharmacy, Shenyang Pharmaceutical University, PO Box No. 122, 103 Wenhua Road, Shenyang 110016, China.
authors: Tiantian
authors: T
authors: Ye
authors: College of Life Science and Biopharmaceutical, Shenyang Pharmaceutical University, PO Box No. 122, 103 Wenhua Road, Shenyang 110016, China.
authors: Xuewei
authors: X
authors: Jiang
authors: Department of Endocrinology, The First Hospital Affiliated to China Medical University, Shenyang 110001, China.
authors: Jing
authors: J
authors: Li
authors: School of Pharmacy, Shenyang Pharmaceutical University, PO Box No. 122, 103 Wenhua Road, Shenyang 110016, China.
authors: Rui
authors: R
authors: Yang
authors: School of Pharmacy, Shenyang Pharmaceutical University, PO Box No. 122, 103 Wenhua Road, Shenyang 110016, China.
authors: Yuling
authors: Y
authors: Mao
authors: School of Pharmacy, Shenyang Pharmaceutical University, PO Box No. 122, 103 Wenhua Road, Shenyang 110016, China.
authors: Kai
authors: K
authors: Li
authors: School of Pharmacy, Shenyang Pharmaceutical University, PO Box No. 122, 103 Wenhua Road, Shenyang 110016, China.
authors: Liang
authors: L
authors: Li
authors: School of Pharmacy, Shenyang Pharmaceutical University, PO Box No. 122, 103 Wenhua Road, Shenyang 110016, China.
authors: Fen
authors: F
authors: Chen
authors: School of Pharmacy, Shenyang Pharmaceutical University, PO Box No. 122, 103 Wenhua Road, Shenyang 110016, China.
authors: Jianhua
authors: J
authors: Yao
authors: College of Life Science and Biopharmaceutical, Shenyang Pharmaceutical University, PO Box No. 122, 103 Wenhua Road, Shenyang 110016, China.
authors: Yingliang
authors: Y
authors: Wu
authors: School of Pharmacy, Shenyang Pharmaceutical University, PO Box No. 122, 103 Wenhua Road, Shenyang 110016, China.
authors: Xinggang
authors: X
authors: Yang
authors: School of Pharmacy, Shenyang Pharmaceutical University, PO Box No. 122, 103 Wenhua Road, Shenyang 110016, China. Electronic address: Wangshujun007@hotmail.com.
authors: Shujun
authors: S
authors: Wang
authors: School of Pharmacy, Shenyang Pharmaceutical University, PO Box No. 122, 103 Wenhua Road, Shenyang 110016, China. Electronic address: pppwwwsss@163.com.
authors: Weisan
authors: W
authors: Pan
mesh_terms: D000818:Animals; D001692:Biological Transport; D045744:Cell Line, Tumor; D065546:Drug Liberation; D004355:Drug Stability; D015972:Gene Expression Regulation, Neoplastic; D005966:Glucuronidase / Q000378:metabolism*; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008081:Liposomes; D008198:Lymph Nodes / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D008207:Lymphatic Metastasis; D051379:Mice; D049329:Nanostructures; D012039:Regional Blood Flow; D012995:Solubility; D014018:Tissue Distribution; D014867:Water / Q000737:chemistry; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D006495:Heparin, Low-Molecular-Weight; D008081:Liposomes; D014867:Water; D000099175:Heparanase
keywords: Heparanase; Low molecular weight heparin; Lymph node metastasis; Nanoliposome; Targeting