Development of 153Sm-Folate-Polyethyleneimine-Conjugated Chitosan Nanoparticles for Targeted Therapy Publisher Pubmed



Mollarazi E¹ ; Jalilian AR² ; Joharidaha F² ; Atyabi F^{1, 3} Show Affiliations
Source: Journal of Labelled Compounds and Radiopharmaceuticals Published:2015

Abstract

The aim of this study was to develop biocompatible, water-soluble 153Sm-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 1H-NMR, FT-IR analyses for molecular dispersity of folate in the NPs. NPs were spherical with mean diameter below 250nm, polydispersity of below 0.15, and positive zeta potential values. The NP complex (153Sm-CHI-DTPA-g-PEI-FA) was stable at 25°C (6-8h, >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 153Sm through the kidneys. The preliminary imaging studies in 4T1 tumor-bearing mice showed minor uptake up to 96h. The present folic acid that functionalized chitosan NP is a candidate material for folate receptor therapy. 153Sm-CHI-DTPA-g-PEI-FA nanoparticles were prepared in >90% radiochemical purity demonstrating folate receptor specific binding in MCF-7 cells and major renal excretion. The imaging studies in 4T1 tumor-bearing mice demonstrated detectable uptake. Copyright © 2015 John Wiley & Sons, Ltd.