title: 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. 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.
  
  
  BACKGROUND
  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.
authors.affiliation: Department of Biomedical Engineering, Florida International University, Miami, Florida, USA.
authors.forename: Tingjun
authors.initials: T
authors.lastname: Lei
authors.forename: Supriya
authors.initials: S
authors.lastname: Srinivasan
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tang
authors.forename: Romila
authors.initials: R
authors.lastname: Manchanda
authors.forename: Abhignyan
authors.initials: A
authors.lastname: Nagesetti
authors.forename: Alicia
authors.initials: A
authors.lastname: Fernandez-Fernandez
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: McGoron
mesh_terms: D000906:Antibodies / Q000276:immunology; D001692:Biological Transport / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D004317:Doxorubicin / Q000494:pharmacology; D004337:Drug Carriers / Q000633:toxicity*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004705:Endocytosis / Q000187:drug effects*; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008027:Light; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D012542:Scattering, Radiation; D055672:Static Electricity; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D000906:Antibodies; D004337:Drug Carriers; D004317:Doxorubicin