Comparing cellular uptake and cytotoxicity of targeted drug carriers in cancer cell lines with different drug resistance mechanisms

Abstract The purpose of this study was to compare the cellular uptake and cytotoxicity of targeted and nontargeted doxorubicin (DOX)-loaded poly(d,l-lactide co -glycolide) (PLGA) nanoparticle (NP) drug delivery systems in drug-resistant ovarian (SKOV-3) and uterine (MES-SA/Dx5) cancer cell lines. Th...

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Veröffentlicht in:Nanomedicine 2011-06, Vol.7 (3), p.324-332
Hauptverfasser: Lei, Tingjun, BS, Srinivasan, Supriya, MS, Tang, Yuan, PhD, Manchanda, Romila, PhD, Nagesetti, Abhignyan, MS, Fernandez-Fernandez, Alicia, DPT, McGoron, Anthony J., PhD
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container_issue 3
container_start_page 324
container_title Nanomedicine
container_volume 7
creator Lei, Tingjun, BS
Srinivasan, Supriya, MS
Tang, Yuan, PhD
Manchanda, Romila, PhD
Nagesetti, Abhignyan, MS
Fernandez-Fernandez, Alicia, DPT
McGoron, Anthony J., PhD
description Abstract The purpose of this study was to compare the cellular uptake and cytotoxicity of targeted and nontargeted doxorubicin (DOX)-loaded poly(d,l-lactide co -glycolide) (PLGA) nanoparticle (NP) drug delivery systems in drug-resistant ovarian (SKOV-3) and uterine (MES-SA/Dx5) cancer cell lines. The cellular uptakes of DOX from nonconjugated DOX-loaded NPs (DNPs) and from HER-2 antibody–conjugated DOX-loaded NPs (ADNPs) in MES-SA/Dx5 cancer cells were higher compared to free DOX. Results also showed higher uptake of DOX from ADNPs in SKOV-3 cells compared with both free DOX and DNPs treatment. Cytotoxicity results at 10 μM extracellular DOX concentration were consistent with the cellular uptake results. Our study concludes that cellular uptake and cytotoxicity of DOX can be improved in MES-SA/Dx5 cells by loading DOX into PLGA NPs. DNPs targeted to membrane receptors may enhance cellular uptake and cytotoxicity in SKOV-3 cells. From the Clinical Editor The authors of this study compare the cellular uptake and cytotoxicity of targeted and nontargeted doxorubicin loaded PLGA nanoparticle delivery systems in drug-resistant ovarian and uterine cancer cell lines, concluding that cellular uptake and cytotoxicity of doxorubicin can be improved by the proposed methods.
doi_str_mv 10.1016/j.nano.2010.11.004
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The cellular uptakes of DOX from nonconjugated DOX-loaded NPs (DNPs) and from HER-2 antibody–conjugated DOX-loaded NPs (ADNPs) in MES-SA/Dx5 cancer cells were higher compared to free DOX. Results also showed higher uptake of DOX from ADNPs in SKOV-3 cells compared with both free DOX and DNPs treatment. Cytotoxicity results at 10 μM extracellular DOX concentration were consistent with the cellular uptake results. Our study concludes that cellular uptake and cytotoxicity of DOX can be improved in MES-SA/Dx5 cells by loading DOX into PLGA NPs. DNPs targeted to membrane receptors may enhance cellular uptake and cytotoxicity in SKOV-3 cells. From the Clinical Editor The authors of this study compare the cellular uptake and cytotoxicity of targeted and nontargeted doxorubicin loaded PLGA nanoparticle delivery systems in drug-resistant ovarian and uterine cancer cell lines, concluding that cellular uptake and cytotoxicity of doxorubicin can be improved by the proposed methods.</description><identifier>ISSN: 1549-9634</identifier><identifier>EISSN: 1549-9642</identifier><identifier>DOI: 10.1016/j.nano.2010.11.004</identifier><identifier>PMID: 21094277</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Antibodies - immunology ; Apoptosis ; Biological Transport - drug effects ; Cell Death - drug effects ; Cell Line, Tumor ; Chemistry, Pharmaceutical ; Cytotoxicity ; Doxorubicin ; Doxorubicin - pharmacology ; Drug Carriers - toxicity ; Drug Resistance, Neoplasm - drug effects ; Endocytosis - drug effects ; HER-2 antibody ; Humans ; Internal Medicine ; Intracellular Space - drug effects ; Intracellular Space - metabolism ; Kinetics ; Light ; Microscopy, Confocal ; Nanoparticles - chemistry ; P-glycoprotein ; Particle Size ; PLGA ; Scattering, Radiation ; Static Electricity ; Subcellular Fractions - metabolism</subject><ispartof>Nanomedicine, 2011-06, Vol.7 (3), p.324-332</ispartof><rights>Elsevier Inc.</rights><rights>2011 Elsevier Inc.</rights><rights>Copyright © 2011 Elsevier Inc. 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The cellular uptakes of DOX from nonconjugated DOX-loaded NPs (DNPs) and from HER-2 antibody–conjugated DOX-loaded NPs (ADNPs) in MES-SA/Dx5 cancer cells were higher compared to free DOX. Results also showed higher uptake of DOX from ADNPs in SKOV-3 cells compared with both free DOX and DNPs treatment. Cytotoxicity results at 10 μM extracellular DOX concentration were consistent with the cellular uptake results. Our study concludes that cellular uptake and cytotoxicity of DOX can be improved in MES-SA/Dx5 cells by loading DOX into PLGA NPs. DNPs targeted to membrane receptors may enhance cellular uptake and cytotoxicity in SKOV-3 cells. 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source MEDLINE; Elsevier ScienceDirect Journals
subjects Antibodies - immunology
Apoptosis
Biological Transport - drug effects
Cell Death - drug effects
Cell Line, Tumor
Chemistry, Pharmaceutical
Cytotoxicity
Doxorubicin
Doxorubicin - pharmacology
Drug Carriers - toxicity
Drug Resistance, Neoplasm - drug effects
Endocytosis - drug effects
HER-2 antibody
Humans
Internal Medicine
Intracellular Space - drug effects
Intracellular Space - metabolism
Kinetics
Light
Microscopy, Confocal
Nanoparticles - chemistry
P-glycoprotein
Particle Size
PLGA
Scattering, Radiation
Static Electricity
Subcellular Fractions - metabolism
title Comparing cellular uptake and cytotoxicity of targeted drug carriers in cancer cell lines with different drug resistance mechanisms
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