title: The lysosomotropic agent, hydroxychloroquine, delivered in a biodegradable nanoparticle system, overcomes drug resistance of B-chronic lymphocytic leukemia cells in vitro.
abstract: Nonviral delivery systems are relatively easy to produce in the large scale, are safe, and elicit a negligible immune response. Nanoparticles (NPs) offer promise as nonviral vectors as biocompatible and -degradable carriers of drugs with targeting to specific sites by surface receptors of monoclonal antibodies (mAbs). We investigated the effect of four PEG-PLGA (polyethylene glycol-polylactic-co-glycolic acid) NP systems on drug-resistant B-chronic lymphocytic leukemia (B-CLL) cells in vitro, three of them encapsulating the drug, hydroxylchloroquine (HDQ), two with NP surface coatings of mAbs (NP1) CD20, (NP2) CD19, and CD20, and one (NP3) with no mAb, but tagged with the fluorescent marker, fluorescein isothiocyanate. The fourth NP system (NP4) was coated with anti-CD19/FITC and anti-CD20/Alexa-Fluor((R)) antibodies, but did not contain the active drug, HCQ. Our data indicate that PEG-PLGA nanoparticles with surface mAbs are suitable for selective drug delivery to B-CLL cells and produce a strong apoptotic effect when loaded with the lysosomotropic agent, HDQ.
authors.affiliation: CUCAIBA, Ministry of Health, Ensenada, Argentina.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Mansilla
authors.forename: Gustavo H
authors.initials: GH
authors.lastname: Marin
authors.forename: Luis
authors.initials: L
authors.lastname: Nuñez
authors.forename: Hugo
authors.initials: H
authors.lastname: Drago
authors.forename: Flavio
authors.initials: F
authors.lastname: Sturla
authors.forename: Carol
authors.initials: C
authors.lastname: Mertz
authors.forename: Luis
authors.initials: L
authors.lastname: Rivera
authors.forename: Thomas
authors.initials: T
authors.lastname: Ichim
authors.forename: Neil
authors.initials: N
authors.lastname: Riordan
authors.forename: Clemente
authors.initials: C
authors.lastname: Raimondi
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm; D006801:Humans; D006886:Hydroxychloroquine / Q000008:administration & dosage*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000008:administration & dosage*; D013050:Spectrometry, Fluorescence
chemical_list: D006886:Hydroxychloroquine