CD19-Targeted Nanodelivery of Doxorubicin Enhances
Therapeutic Efficacy in B‑Cell Acute Lymphoblastic Leukemia
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Abstract
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