The lysosomotropic agent, hydroxychloroquine, delivered in a biodegradable nanoparticle system, overcomes drug resistance of B-chronic lymphocytic leukemia cells in vitro

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...

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Published inCancer biotherapy & radiopharmaceuticals Vol. 25; no. 1; pp. 97 - 103
Main Authors Mansilla, Eduardo, Marin, Gustavo H, Nuñez, Luis, Drago, Hugo, Sturla, Flavio, Mertz, Carol, Rivera, Luis, Ichim, Thomas, Riordan, Neil, Raimondi, Clemente
Format Journal Article
LanguageEnglish
Published United States Mary Ann Liebert, Inc 01.02.2010
Subjects
Cell Survival - drug effects
Drug Delivery Systems
Drug resistance
Drug Resistance, Neoplasm
Drug therapy
Health aspects
Humans
Hydroxychloroquine
Hydroxychloroquine - administration & dosage
Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy
Leukemia, Lymphocytic, Chronic, B-Cell - pathology
Lymphocytic leukemia
Microscopy, Confocal
Nanoparticles
Nanoparticles - administration & dosage
Spectrometry, Fluorescence
United States
Argentina
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Summary: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.
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ISSN:1084-9785
1557-8852
DOI:10.1089/cbr.2009.0655