Nanotechnology approaches have tremendous potential for enhancing treatment
efficacy with lower doses of chemotherapeutics. Nanoparticle-based drug delivery
approaches are poorly developed for childhood leukemia. Dexamethasone (Dex) is one of the
most common chemotherapeutic drugs used in the treatment of childhood leukemia. In this
study, we encapsulated Dex in polymeric nanoparticles and validated their anti-leukemic
potential in vitro and in vivo. Nanoparticles (NPs) with
an average diameter of 110 nm were assembled from amphiphilic block copolymers poly
(ethylene glycol) (PEG) and poly (ε-caprolactone) (PCL) bearing pendant cyclic
ketals. The blank nanoparticles were non-toxic to cultured cells in vitro
and to mice in vivo. Encapsulation of Dex into the nanoparticles (Dex-NP)
did not compromise the bioactivity of the drug. Dex-NPs induced glucocorticoid
phosphorylation and showed cytotoxicity similar to the free Dex in leukemic cells. Studies
using nanoparticles labeled with fluorescent dyes revealed leukemic cell surface binding
and internalization. In vivo biodistribution studies showed NP
accumulation in the liver and spleen with subsequent clearance of the particles with time.
In a pre-clinical model of leukemia, Dex-NPs significantly improved the quality of life
and survival of mice compared to the free drug. To our knowledge, this is the first report
showing the efficacy of polymeric nanoparticles to deliver Dex to potentially treat
childhood leukemia and reveals that low dose of Dex should be sufficient for inducing cell
death and improve survival.
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