2 research outputs found
CD19-Targeted Nanodelivery of Doxorubicin Enhances Therapeutic Efficacy in B‑Cell Acute Lymphoblastic Leukemia
Nanomedicine
has advanced to clinical trials for adult cancer therapy.
However, the field is still in its infancy for treatment of childhood
malignancies such as acute lymphoblastic leukemia (ALL). Nanotherapy
offers multiple advantages over conventional therapy. It facilitates
targeted delivery and enables controlled release of drugs to reduce
treatment-related side effects. Here, we demonstrate that doxorubicin
(DOX) encapsulated in polymeric nanoparticles (NPs) modified with
targeting ligands against CD19 (CD19-DOX-NPs) can be delivered in
a CD19-specific manner to leukemic cells. The CD19-DOX-NPs were internalized
via receptor-mediated endocytosis and imparted cytotoxicity in a CD19-dependent
manner in CD19-positive ALL cells. Leukemic mice treated with CD19-DOX-NPs
survived significantly longer and manifested a higher degree of agility,
indicating reduced apparent systemic toxicity during treatment compared
to mice treated with free DOX. We suggest that targeted delivery of
drugs used in childhood cancer treatment should improve therapeutic
efficacy and reduce treatment-related side effects in children
Dexamethasone-Loaded Block Copolymer Nanoparticles Induce Leukemia Cell Death and Enhance Therapeutic Efficacy: A Novel Application in Pediatric Nanomedicine
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 polyÂ(ethylene
glycol) (PEG) and polyÂ(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