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

• Published in: Nanomedicine Vol. 7; no. 3; pp. 324 - 332
• Main Authors: Lei, Tingjun, BS, Srinivasan, Supriya, MS, Tang, Yuan, PhD, Manchanda, Romila, PhD, Nagesetti, Abhignyan, MS, Fernandez-Fernandez, Alicia, DPT, McGoron, Anthony J., PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2011
• 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; P-glycoprotein; Cytotoxicity; PLGA; HER-2 antibody; Doxorubicin; Apoptosis
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2010.11.004

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.