title: Simultaneous delivery of chemotherapeutic and thermal-optical agents to cancer cells by a polymeric (PLGA) nanocarrier: an in vitro study.
abstract: OBJECTIVE
  To test the effectiveness of a dual-agent-loaded PLGA nanoparticulate drug delivery system containing doxorubicin (DOX) and indocyanine green (ICG) in a DOX-sensitive cell line and two resistant cell lines that have different resistance mechanisms.
  
  
  METHODS
  The DOX-sensitive MES-SA uterine sarcoma cell line was used as a negative control. The two resistant cell lines were uterine sarcoma MES-SA/Dx5, which overexpresses the multidrug resistance exporter P-glycoprotein, and ovarian carcinoma SKOV-3, which is less sensitive to doxorubicin due to a p53 gene mutation. The cellular uptake, subcellular localization and cytotoxicity of the two agents when delivered via nanoparticles (NPs) were compared to their free-form administration.
  
  
  RESULTS
  The cellular uptake and cytotoxicity of DOX delivered by NPs were comparable to the free form in MES-SA and SKOV-3, but much higher in MES-SA/Dx5, indicating the capability of the NPs to overcome P-glycoprotein resistance mechanisms. NP-encapsulated ICG showed slightly different subcellular localization, but similar fluorescence intensity when compared to free ICG, and retained the ability to generate heat for hyperthermia delivery.
  
  
  CONCLUSIONS
  The dual-agent-loaded system allowed for the simultaneous delivery of hyperthermia and chemotherapy, and this combinational treatment greatly improved cytotoxicity in MES-SA/Dx5 cells and to a lesser extent in SKOV-3 cells.
authors.affiliation: Department of Biomedical Engineering, Florida International University, 10555 West Flagler Street, Miami, Florida 33174, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tang
authors.forename: Tingjun
authors.initials: T
authors.lastname: Lei
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: Supriya
authors.initials: S
authors.lastname: Srinivasan
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: McGoron
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001692:Biological Transport; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods; D019344:Lactic Acid / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry*; D055620:Optical Phenomena; D009930:Organic Chemicals / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012995:Solubility; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D009930:Organic Chemicals; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004317:Doxorubicin; C035709:iodocyanine green