Doxorubicin loaded polymeric gold nanoparticles targeted to human folate receptor upon laser photothermal therapy potentiates chemotherapy in breast cancer cell lines

• Published in: Journal of photochemistry and photobiology. B, Biology Biology, 2015-08, Vol.149, p.116-128
• Main Authors: Banu, Hussaina, Sethi, Dipinder Kaur, Edgar, Andre, Sheriff, Adhnaan, Rayees, Nuthan, Renuka, N., Faheem, S.M., Premkumar, Kumpati, Vasanthakumar, Geetha
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; Apoptosis - radiation effects; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cell Line, Tumor; Doxorubicin; Doxorubicin - chemistry; Doxorubicin - pharmacology; Doxorubicin - therapeutic use; Drug delivery; Drug Liberation; Drug Stability; Folate; Folic Acid - chemistry; Folic Acid Transporters - metabolism; Gold - chemistry; Gold nanoparticles; Humans; Kinetics; Laser Therapy; Metal Nanoparticles - chemistry; Molecular Targeted Therapy; Necrosis; Phototherapy; Photothermal therapy; Polyethylene Glycols - chemistry; Polymers - chemistry; Proto-Oncogene Proteins c-bcl-2 - metabolism; Sulfonic Acids - chemistry; Surface Properties; Tumor Suppressor Protein p53 - metabolism
• ISSN: 1011-1344; 1873-2682
• DOI: 10.1016/j.jphotobiol.2015.05.008

[Display omitted] •Folate and doxorubicin conjugated polymeric gold nanoparticles for cancer treatment.•Targeted to folate receptor overexpressing cancer cells & suited for hyperthermia.•Combination modality of targeted chemotherapy & hyperthermia investigated in vitro.•Bioconjugation of nanoparticles characterized and apoptotic cell death studied.•Up-regulated pro-apoptotic p53 & down-regulated anti-apoptotic Bcl-2 proteins noted. The current research focuses on the application of folate conjugated and doxorubicin loaded polymeric gold nanoparticles (GNPs) for the targeted treatment of folate receptor overexpressing breast cancers, augmented by adjunctive laser photothermal therapy. Herein, GNPs surface modified with folate, drug doxorubicin and polyethylene glycol were engineered and were used as vehicles for folate receptor targeted delivery of doxorubicin into cancer cells. Subsequently, the GNPs were photo-excited using laser light for mediating hyperthermia in the cancer cells. In vitro studies were performed to validate the efficacy of the combined modality of folate conjugated and doxorubicin loaded polymeric GNP mediated chemotherapy followed by photothermal therapy in comparison to treatment with free drug; and the combination modality showed better therapeutic efficacy than that of plain doxorubicin treatment in MDA-MB-231 breast cancer cells that express increased levels of surface folate receptors when compared to MCF-7 breast cancer cells that express low levels of folate receptor. The mechanism of cell death was investigated using fluorescent microscopy. Immunoassays showed the up-regulation of the pro-apoptotic protein p53 and down-regulation of the anti-apoptotic protein Bcl-2. Collectively, these results suggest that the folate tagged doxorubicin loaded GNPs are an attractive platform for targeted delivery of doxorubicin and are agents suitable for photothermal cancer therapy.