Targeted nanoparticles for simultaneous delivery of chemotherapeutic and hyperthermia agents--an in vitro study

The purpose of this study was to prepare targeted Poly lactide-co-glycolide (PLGA) nanoparticles with simultaneous entrapment of indocyanine green (ICG) and doxorubicin (DOX) by surface decorating them with tumor specific monoclonal antibodies in order to achieve simultaneous therapy and imaging. ICG was chosen as an imaging and hyperthermia agent and DOX was used as a chemotherapeutic agent. ICG and DOX were incorporated into PLGA nanoparticles using the oil-in-water emulsion solvent evaporation technique. These nanoparticles were further surface decorated with antibodies against Human Epithelial Receptor-2 (HER-2) using carbodiimide chemistry. The uptake of antibody conjugated ICG-DOX-PLGA nanoparticles (AIDNP) was enhanced in SKOV-3 (HER-2 overexpressing cell lines) compared to their non-conjugated counterparts (ICG-DOX-PLGA nanoparticles (IDNP)). The uptake of antibody conjugated ICG-DOX-PLGA nanoparticles, however, was similar in MES-SA and MES-SA/Dx5 cancer cells (HER-2 negative cell lines), which were used as negative controls. The cytotoxicity results after laser treatment (808 nm, 6.7 W/cm(2)) showed an enhanced toxicity in treatment of SKOV-3. The negative controls exhibited comparable cytotoxicity with or without exposure to the laser. Thus, this study showed that these antibody conjugated ICG-DOX-PLGA nanoparticles have potential for combinatorial chemotherapy and hyperthermia.