title: Docetaxel (DTX)-loaded polydopamine-modified TPGS-PLA nanoparticles as a targeted drug delivery system for the treatment of liver cancer.
abstract: Polydopamine-based surface modification is a simple way to functionalize polymeric nanoparticle (NP) surfaces with ligands and/or additional polymeric layers. In this work, we developed DTX-loaded formulations using polydopamine-modified NPs synthesized using D-α-tocopherol polyethylene glycol 1000 succinate-poly(lactide) (pD-TPGS-PLA/NPs). To target liver cancer cells, galactosamine was conjugated on the prepared NPs (Gal-pD-TPGS-PLA/NPs) to enhance the delivery of DTX via ligand-mediated endocytosis. The size and morphology of pD-TPGS-PLA/NPs and Gal-pD-TPGS-PLA/NPs changed obviously compared with TPGS-PLA/NPs. In vitro studies showed that TPGS-PLA/NPs, pD-TPGS-PLA/NPs and Gal-pD-TPGS-PLA/NPs had similar release profiles of DTX. Both confocal laser scanning microscopy and flow cytometric results showed that coumarin 6-loaded Gal-pD-TPGS-PLA/NPs had the highest cellular uptake efficiency in liver cancer cell line HepG2. Moreover, DTX-loaded Gal-pD-TPGS-PLA/NPs inhibited the growth of HepG2 cells more potently than TPGS-PLA/NPs, pD-TPGS-PLA/NPs, and a clinically available DTX formulation (Taxotere®). The in vivo biodistribution experiments show that the Gal-pD-TPGS-PLA/NPs are specifically targeted to the tumor. Furthermore, the in vivo anti-tumor effects study showed that injecting DTX-loaded Gal-pD-TPGS-PLA/NPs reduced the tumor size most significantly on hepatoma-bearing nude mice. These results suggest that Gal-pD-TPGS-PLA/NPs prepared in the study specifically interacted with the hepatocellular carcinoma cells through ligand-receptor recognition and they may be used as a potentially eligible drug delivery system targeting liver cancers.
  
  
  CONCLUSIONS
  Polydopamine-based surface modification is a simple way to functionalize polymeric nanoparticle surfaces with ligands and/or additional polymeric layers. In this work, we developed docetaxel (DTX)-loaded formulations using polydopamine-modified NPs synthesized from D-α-tocopherol polyethylene glycol 1000 succinate-poly(lactide) (pD-TPGS-PLA/NPs). To target liver cancer cells, galactosamine was conjugated on the prepared NPs (Gal-pD-TPGS-PLA/NPs) to enhance the delivery of DTX via ligand-mediated endocytosis. Both confocal laser scanning microscopy and flow cytometric results showed that coumarin 6-loaded Gal-pD-TPGS-PLA/NPs had the highest cellular uptake efficiency for liver cancer cell line HepG2. The in vivo biodistribution experiments show that the Gal-pD-TPGS-PLA/NPs are specifically targeted to the tumor. Furthermore, the in vivo anti-tumor effects study showed that injecting DTX-loaded Gal-pD-TPGS-PLA/NPs reduced the tumor size most significantly on hepatoma-bearing nude mice. These results suggest that Gal-pD-TPGS-PLA/NPs prepared in the study specifically interacted with the hepatocellular carcinoma cells through ligand-receptor recognition and they could be used as a potentially eligible drug delivery system targeting liver cancers.
authors.affiliation: Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Biomedical Materials, Tianjin 300192, PR China.
authors.forename: Dunwan
authors.initials: D
authors.lastname: Zhu
authors.affiliation: The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tao
authors.affiliation: The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China; Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, PR China.
authors.forename: Hongling
authors.initials: H
authors.lastname: Zhang
authors.affiliation: The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China.
authors.forename: Gan
authors.initials: G
authors.lastname: Liu
authors.affiliation: The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China.
authors.forename: Teng
authors.initials: T
authors.lastname: Wang
authors.affiliation: Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Biomedical Materials, Tianjin 300192, PR China.
authors.forename: Linhua
authors.initials: L
authors.lastname: Zhang
authors.affiliation: The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China. Electronic address: zeng.xiaowei@sz.tsinghua.edu.cn.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zeng
authors.affiliation: The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China. Electronic address: mei.lin@sz.tsinghua.edu.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Mei
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000077143:Docetaxel; D016503:Drug Delivery Systems / Q000379:methods*; D056945:Hep G2 Cells; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D019344:Lactic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D011091:Polyesters; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D043823:Taxoids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D007211:Indoles; D011091:Polyesters; D011108:Polymers; D043823:Taxoids; C568283:polydopamine; D014810:Vitamin E; D000077143:Docetaxel; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); C014225:tocophersolan
keywords: Cancer nanotechnology; Dopamine polymerization; Galactosylated nanoparticles; Liver targeting; Surface modification