title: Synthesis, pharmacoscintigraphic evaluation and antitumor efficacy of methotrexate-loaded, folate-conjugated, stealth albumin nanoparticles.
abstract: The present study aims to develop a multifunctional nanoformulation based on technetium-99m labeled, folate conjugated, methotrexate-loaded human serum albumin nanoparticles (HSA NPs) and explore their potential in cancer theragnostics.
  
  
  METHODS
  Methotrexate-loaded HSA NPs were synthesized by a reverse microemulsion technique, followed by chemical crosslinking with glutaraldehyde. These NPs were conjugated with folic acid (FA) through a hydrophilic polyethylene glycol spacer to render them long-circulatory and augment their tumor-specific localization. The therapeutic conjugate was further radiolabeled with a γ-emitter technetium-99m for real-time monitoring of its blood clearance kinetics and biodistribution through the measurement of blood/organ-associated radioactivity and scintigraphic imaging.
  
  
  CONCLUSIONS
  In vitro cell-uptake and cytotoxicity studies corroborated that FA conjugation enabled these NPs to specifically target and kill folate-receptor overexpressing cancer cells via S phase arrest. Blood clearance kinetics and biodistribution studies clearly indicated that circulation time, as well as tumor-specific localization of methotrexate-loaded HSA nanocarriers, could be significantly augmented upon polyethylene glycolylation and conjugation of FA. Finally, we demonstrated that these targeted HSA NPs inhibited tumor growth more effectively, as compared with the nontargeted controls.
authors.affiliation: Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, SAS Nagar (Mohali) Punjab 160062, India. sanyogjain@niper.ac.in
authors.forename: Sanyog
authors.initials: S
authors.lastname: Jain
authors.forename: Rashi
authors.initials: R
authors.lastname: Mathur
authors.forename: Manasmita
authors.initials: M
authors.lastname: Das
authors.forename: Nitin K
authors.initials: NK
authors.lastname: Swarnakar
authors.forename: Anil K
authors.initials: AK
authors.lastname: Mishra
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival; D004337:Drug Carriers / Q000138:chemical synthesis*; D004355:Drug Stability; D005492:Folic Acid / Q000032:analysis* / Q000096:biosynthesis; D006367:HeLa Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008727:Methotrexate / Q000032:analysis / Q000493:pharmacokinetics*; D053758:Nanoparticles / Q000737:chemistry*; D012709:Serum Albumin / Q000032:analysis* / Q000096:biosynthesis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013499:Surface Properties; D013668:Technetium Tc 99m Aggregated Albumin / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D000964:Antimetabolites, Antineoplastic; D004337:Drug Carriers; D012709:Serum Albumin; D013668:Technetium Tc 99m Aggregated Albumin; C040811:methotrexate-serum albumin; D005492:Folic Acid; D008727:Methotrexate