Simultaneous delivery of chemotherapeutic and thermal-optical agents to cancer cells by a polymeric (PLGA) nanocarrier: an in vitro study

Pharm Res. 2010 Oct;27(10):2242-53. doi: 10.1007/s11095-010-0231-6. Epub 2010 Aug 6.


Purpose: 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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacokinetics
  • Biological Transport
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Doxorubicin / administration & dosage*
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / pharmacology
  • Drug Carriers / chemistry*
  • Drug Resistance, Neoplasm / drug effects
  • Female
  • Humans
  • Hyperthermia, Induced / methods
  • Lactic Acid / chemistry*
  • Microscopy, Electron, Scanning
  • Nanoparticles / chemistry*
  • Optical Phenomena
  • Organic Chemicals / administration & dosage*
  • Organic Chemicals / pharmacokinetics
  • Organic Chemicals / pharmacology
  • Particle Size
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Solubility
  • Surface Properties


  • Antineoplastic Agents
  • Drug Carriers
  • Organic Chemicals
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Doxorubicin
  • iodocyanine green