A facile strategy for synthesis of a broad palette of intrinsically radiolabeled chitosan nanoparticles for potential use in cancer theranostics

The conventional, chelator-based techniques used for radiolabelling of nanoparticles possess certain shortcomings due to their inherent limitations related to coordination chemistry. These limitations affect their binding with radioisotopes and alter their pharmacokinetics leading to delayed uptake and clearance from the body and possible detachment of radioisotopes during imaging/treatment. These issues have necessitated the development of facile, chelator-free, intrinsic radiolabelling techniques that may obviate any changes in the unique properties of nanomaterials, such as their size and surface charge, resulting in efficacious cancer imaging and therapy. In this work, chitosan, a naturally occurring, non-toxic, biodegradable and biocompatible polymer was complexed with selected diagnostic and therapeutic radioisotopes (64Cu, 68Ga, 90Y, 153Sm, 166Ho and 177Lu). The radiolabelled chitosan was converted into nanoparticles by ionotropic gelation method. The cell uptake and cytotoxicity of the surrogate nanoparticles were evaluated in epithelial lung cancer cells. Biodistribution studies in normal C57BL/6 mice demonstrated high in vivo stability of the intrinsically radiolabeled nanoparticles. Overall, this strategy will empower the development of intrinsically radiolabeled biocompatible nanoplatforms for potential use in cancer theranostics.

Automated summary

Conventional chelator-based techniques for radiolabelling nanoparticles have limitations that affect their binding with radioisotopes and in vivo stability. This study introduces a novel approach using chitosan as an intrinsic radiolabelling agent, allowing for the creation of stable nanoparticles with high biocompatibility and biodistribution.