title: CD19-Targeted Nanodelivery of Doxorubicin Enhances Therapeutic Efficacy in B-Cell Acute Lymphoblastic Leukemia.
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.
authors.affiliation: ⊥Nemours Center for Childhood Cancer Research, A. I. duPont Hospital for Children, Wilmington, Delaware 19803, United States.
authors.forename: Vinu
authors.initials: V
authors.lastname: Krishnan
authors.forename: Xian
authors.initials: X
authors.lastname: Xu
authors.forename: Dakota
authors.initials: D
authors.lastname: Kelly
authors.affiliation: #Pharmacology and Experimental Therapeutics, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, United States.
authors.forename: Adam
authors.initials: A
authors.lastname: Snook
authors.affiliation: #Pharmacology and Experimental Therapeutics, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, United States.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Waldman
authors.affiliation: ⊥Nemours Center for Childhood Cancer Research, A. I. duPont Hospital for Children, Wilmington, Delaware 19803, United States.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Mason
authors.forename: Xinqiao
authors.initials: X
authors.lastname: Jia
authors.affiliation: ∇Therapy Architects, LLC, 2700 Silverside Road, Wilmington, Delaware 19810, United States.
authors.forename: Ayyappan K
authors.initials: AK
authors.lastname: Rajasekaran
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D018941:Antigens, CD19; D004317:Doxorubicin
keywords: CD19; acute leukemia; doxorubicin; endocytosis; nanoparticles; xenograft model