title: LyP-1-conjugated nanoparticles for targeting drug delivery to lymphatic metastatic tumors.
abstract: Active tumor targeting by biodegradable nanoparticles has been widely studied for cancer diagnosis and therapy. However, target-specific nanoparticles for drug delivery to lymphatic metastases have not been reported yet due to the lack of specific markers in the tumor lymphatics. Recently, peptide LyP-1 has been recognized for its specific home to tumors and their lymphatics. In this study, we tested the possibility of LyP-1 serving as a target-specific peptide of PEG-PLGA nanoparticles to tumor lymph metastases. LyP-1 was synthesized by using Boc-protected amino acids. The copolymers of maleimide-PEG-PLGA were formed by the conjugation of maleimide-PEG-NH(2) to PLGA-COOH, which were applied to prepare pegylated nanoparticles with mPEG-PLGA by means of double emulsion/solvent evaporation technique. LyP-1 with sulfhydryl group was conjugated to the maleimide function located at the distal end of PEG surrounding the nanoparticle surface. LyP-1-conjugated PEG-PLGA nanoparticle (LyP-1-NPs) had a round and regular shape with a diameter around 90 nm. In vitro, cellular uptake of LyP-1-NPs was about four times of that of PEG-PLGA nanoparticles without LyP-1 (NPs). In vivo, the uptake of LyP-1-NPs in metastasis lymph nodes was about eight times of that of NPs. This study indicates that LyP-1-NP is a promising carrier for target-specific drug delivery to lymphatic metastatic tumors.
authors.affiliation: Pancreatic Disease Institute, Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Guopei
authors.initials: G
authors.lastname: Luo
authors.forename: Xianjun
authors.initials: X
authors.lastname: Yu
authors.forename: Chen
authors.initials: C
authors.lastname: Jin
authors.forename: Feng
authors.initials: F
authors.lastname: Yang
authors.forename: Deliang
authors.initials: D
authors.lastname: Fu
authors.forename: Jiang
authors.initials: J
authors.lastname: Long
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.forename: Changyou
authors.initials: C
authors.lastname: Zhan
authors.forename: Weiyue
authors.initials: W
authors.lastname: Lu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D001692:Biological Transport; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D006801:Humans; D008198:Lymph Nodes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D008301:Maleimides / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D010316:Particle Size; D010456:Peptides, Cyclic / Q000737:chemistry / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011098:Polyglactin 910 / Q000737:chemistry*; D011485:Protein Binding; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; C533969:LyP-1 peptide; D008301:Maleimides; D010456:Peptides, Cyclic; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D011098:Polyglactin 910; D011092:Polyethylene Glycols