title: Internalization and subcellular fate of aptamer and peptide dual-functioned nanoparticles.
abstract: OBJECTIVE
  To evaluate the internalization and subcellular fate of AS1411 aptamer (for glioma targeting) and TGN peptide (for blood-brain barrier targeting)-modified nanoparticles (AsTNPs), which was important for optimizing targeted delivery systems and realizing the potential toxicity to cells.
  
  
  METHODS
  Organelles were labelled with specific markers. Several uptake inhibitors were used to determine the endocytosis pathways. Transmission electron microscopy (TEM) was utilized to directly observe the endocytosis procedure and subcellular fate of AsTNPs.
  
  
  RESULTS
  Subcellular localization demonstrated that endosomes and mitochondria were involved in the uptake of AsTNPs by both C6 and bEnd.3 cells, however, lysosomes and Golgi apparatus were only involved in the internalization by C6 cells rather than bEnd.3 cells. Uptake mechanism study demonstrated the clathrin- and caveolae-mediated endocytosis were the main pathways in the uptake of AsTNPs by C6 and bEnd.3 cells. However, other pathways, including clathrin- and caveolae-independent endocytosis and macropinocytosis are also involved in the uptake by C6 cells and not by bEnd.3 cells. TEM directly demonstrated the involvement of these pathways. Particles could be found mostly in endosomes.
  
  
  CONCLUSIONS
  Compared to unmodified nanoparticles, AsTNPs displayed different internalization pathways involved in several cell organelles.
authors: Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University , Shanghai , China.
authors: Huile
authors: H
authors: Gao
authors: Zhi
authors: Z
authors: Yang
authors: Shuang
authors: S
authors: Zhang
authors: Zhiqing
authors: Z
authors: Pang
authors: Xinguo
authors: X
authors: Jiang
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001932:Brain Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D004705:Endocytosis / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005910:Glioma / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D051379:Mice; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010316:Particle Size; D010455:Peptides / Q000737:chemistry*; D013347:Subcellular Fractions / Q000187:drug effects* / Q000378:metabolism; D013499:Surface Properties
chemical_list: C513936:AGRO 100; D052157:Aptamers, Nucleotide; D004337:Drug Carriers; D009838:Oligodeoxyribonucleotides; D010455:Peptides
keywords: Dual-targeting delivery system; internalization; subcellular fate; uptake mechanism