title: Development of (153) Sm-folate-polyethyleneimine-conjugated chitosan nanoparticles for targeted therapy.
abstract: The aim of this study was to develop biocompatible, water-soluble (153) Sm-labeled chitosan nanoparticles (NPs) containing folate and polyethyleneimine functionalities i.e. chitosan-graft-PEI-folate (CHI-DTPA-g-PEI-FA), suitable for targeted therapy. The physicochemical properties of the obtained NPs were characterized by dynamic light-scattering analysis for their mean size, size distribution, and zeta potential; scanning electron microscopy for surface morphology; and (1) H-NMR, FT-IR analyses for molecular dispersity of folate in the NPs. NPs were spherical with mean diameter below 250 nm, polydispersity of below 0.15, and positive zeta potential values. The NP complex ((153) Sm-CHI-DTPA-g-PEI-FA) was stable at 25 °C (6-8 h, >90% radiochemical purity, instant thin layer chromatography (ITLC)). Binding studies using fluorescent NPs for internalization also demonstrated significant uptake in MCF-7 cells. MCF-7 cell internalization was significantly greater for 4T1. In blocking studies, both MCF-7 and 4T1 cell lines demonstrated specific folate receptor (FR) binding (decreasing 45%). In vivo biodistribution studies indicated major excretion of NPs metabolites and/or free (153) Sm through the kidneys. The preliminary imaging studies in 4T1 tumor-bearing mice showed minor uptake up to 96 h. The present folic acid that functionalized chitosan NP is a candidate material for folate receptor therapy.
authors.affiliation: Food and Drug Control Laboratories and Food and Drug Laboratory Research Centre, MOHME, Tehran, Iran.
authors.forename: Esmail
authors.initials: E
authors.lastname: Mollarazi
authors.affiliation: Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), Tehran, 14155-1339, Iran.
authors.forename: Amir R
authors.initials: AR
authors.lastname: Jalilian
authors.affiliation: Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), Tehran, 14155-1339, Iran.
authors.forename: Fariba
authors.initials: F
authors.lastname: Johari-Daha
authors.affiliation: Food and Drug Control Laboratories and Food and Drug Laboratory Research Centre, MOHME, Tehran, Iran.|Medical Nanotechnology Research Centre, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Atyabi
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry; D004337:Drug Carriers; D005260:Female; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D011094:Polyethyleneimine / Q000031:analogs & derivatives* / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000737:chemistry* / Q000493:pharmacokinetics; D012493:Samarium / Q000737:chemistry* / Q000493:pharmacokinetics; D017550:Spectroscopy, Fourier Transform Infrared; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D019275:Radiopharmaceuticals; C551320:chitosan-graft-polyethylenimine; D012493:Samarium; C061972:samarium Sm-153 lexidronam; D011094:Polyethyleneimine; D048271:Chitosan; D005492:Folic Acid
keywords: 153Sm; 4T1; MCF-7; SPECT; biodistribution; breast cancer; chitosan nanoparticles; folate receptor