Dexamethasone-Loaded Block
Copolymer Nanoparticles
Induce Leukemia Cell Death and Enhance Therapeutic Efficacy: A Novel
Application in Pediatric Nanomedicine
- Publication date
- Publisher
Abstract
Nanotechnology approaches have tremendous potential for
enhancing
treatment efficacy with lower doses of chemotherapeutics. Nanoparticle
(NP)-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 NPs and validated their antileukemic
potential in vitro and in vivo. NPs with an average diameter of 110
nm were assembled from an amphiphilic block copolymer of poly(ethylene
glycol) (PEG) and poly(ε-caprolactone) (PCL) bearing pendant
cyclic ketals (ECT2). The blank NPs were nontoxic to cultured cells
in vitro and to mice in vivo. Encapsulation of Dex into the NPs (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 NPs 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 preclinical model of leukemia,
Dex-NPs significantly improved the quality of life and survival of
mice as compared to the free drug. To our knowledge, this is the first
report showing the efficacy of polymeric NPs to deliver Dex to potentially
treat childhood leukemia and reveals that low doses of Dex should
be sufficient for inducing cell death and improving survival