title: Targeted delivery of doxorubicin-utilizing chitosan nanoparticles surface-functionalized with anti-Her2 trastuzumab.
abstract: BACKGROUND
  Targeting drugs to their sites of action to overcome the systemic side effects associated with most antineoplastic agents is still a major challenge in pharmaceutical research. In this study, the monoclonal antibody, trastuzumab, was used as a targeting agent in nanoparticles carrying the antitumor drug, doxorubicin, specifically to its site of action.
  
  
  METHODS
  Chitosan-doxorubicin conjugation was carried out using succinic anhydride as a crosslinker. Trastuzumab was conjugated to self-assembled chitosan-doxorubin conjugate (CS-DOX) nanoparticles (particle size, 200 nm) via thiolation of lysine residues and subsequent linking of the resulted thiols to chitosan. Conjugation was confirmed by gel permeation chromatography, differential scanning calorimetry, Fourier transform infrared spectroscopy, and (1)H nuclear magnetic resonance spectroscopy studies. Dynamic light scattering, transmission electron microscopy, and zeta potential determination were used to characterize the nanoparticles.
  
  
  RESULTS
  CS-DOX conjugated nanoparticles had a spherical shape and smooth surface with a narrow size distribution and core-shell structure. Increasing the ratio of doxorubicin to chitosan in the conjugation reaction gave rise to a higher doxorubicin content but lower conjugation efficiency. Trastuzumab-decorated nanoparticles (CS-DOX-mAb) contained 47 μg/mg doxorubicin and 33.5 μg/mg trastuzumab. Binding of trastuzumab to the nanoparticles was further probed thermodynamically by isothermal titration calorimetry. Fluorescence microscopy demonstrated enhanced and selective uptake of CS-DOX-mAb by Her2+ cancer cells compared with nontargeted CS-DOX nanoparticles and free drug.
  
  
  CONCLUSIONS
  Antibody-conjugated nanoparticles were shown to discriminate between Her2+ and Her2⁻ cells, and thus have the potential to be used in active targeted drug delivery, with reduction of drug side effects in Her2+ breast and ovarian cancers.
authors: Department of Biotechnology, Faculty of Science, University of Tehran, Tehran, Iran.
authors: Parisa
authors: P
authors: Yousefpour
authors: Fatemeh
authors: F
authors: Atyabi
authors: Ebrahim
authors: E
authors: Vasheghani-Farahani
authors: Ali-Akbar Mousavi
authors: AA
authors: Movahedi
authors: Rassoul
authors: R
authors: Dinarvand
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D048271:Chitosan / Q000737:chemistry; D004317:Doxorubicin / Q000737:chemistry / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D058726:Nanoconjugates / Q000737:chemistry* / Q000627:therapeutic use; D010051:Ovarian Neoplasms / Q000188:drug therapy; D010316:Particle Size; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology; D000068878:Trastuzumab
chemical_list: D000903:Antibiotics, Antineoplastic; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D048271:Chitosan; D004317:Doxorubicin; D058726:Nanoconjugates; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab