Development of 153Sm-folate-polyethyleneimine-conjugated chitosan nanoparticles for targeted therapy

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 250 nm, polydispersity of below 0.15, and positive zeta potential values. The NP complex (153Sm‐CHI‐DTPA‐g‐PEI‐FA) was stable at 25 °C (6–8 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 153Sm 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. 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.