Dexamethasone-Loaded Block Copolymer Nanoparticles Induce Leukemia Cell Death and Enhance Therapeutic Efficacy: A Novel Application in Pediatric Nanomedicine

Department of Materials Science and Engineering, University of Delaware , 201 DuPont Hall, Newark, Delaware 19716-1501, United States.
Molecular Pharmaceutics (Impact Factor: 4.38). 06/2013; 10(6):2199-2210. DOI: 10.1021/mp300350e
Source: PubMed


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.

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Available from: Vinu Krishnan, Dec 19, 2014
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    • "Specially, synthetic amphiphilic block copolymers consisting of hydrophobic core and PEG shell have drawn great interests owing to their excellent biocompatibility.[9] [10] [11] [12] [13] [14] Meanwhile, the low toxicity, the ability to effectively prolong the retention time in blood and then be excreted by kidneys make them safe for medical applications.[15] [16] [17] [18] [19] [20] [21] In particular, NPs formed from PEG and poly (ε-caprolactone) (PCL) block copolymer have been extensively studied due to the fact that PCL is an FDA-approved biodegradable polymer with potential applications in other aspects as biomaterials.[22] "
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    • "Several strategies including the use of nanoparticles have been proposed to avoid these concerns including its long-term impairment of physiological functions (22). A variety of nanoparticles, including dendrimers, gold particles, liposomes, micelles, and polymers have been described to improve the bioavailability or the therapeutic efficacy of currently used anti-cancer agents (14, 16). These nanodelivery systems have yet to be evaluated in pediatric leukemia patients. "
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