title: Optimization of anti-cancer drugs and a targeting molecule on multifunctional gold nanoparticles.
abstract: Breast cancer is the most common and deadly cancer among women worldwide. Currently, nanotechnology-based drug delivery systems are useful for cancer treatment; however, strategic planning is critical in order to enhance the anti-cancer properties and reduce the side effects of cancer therapy. Here, we designed multifunctional gold nanoparticles (AuNPs) conjugated with two anti-cancer drugs, TGF-β1 antibody and methotrexate, and a cancer-targeting molecule, folic acid. First, optimum size and shape of AuNPs was selected by the highest uptake of AuNPs by MDA-MB-231, a metastatic human breast cancer cell line. It was 100 nm spherical AuNPs (S-AuNPs) that were used for further studies. A fixed amount (900 μl) of S-AuNP (3.8 × 10(8) particles/ml) was conjugated with folic acid-BSA or methotrexate-BSA. Methotrexate on S-AuNP induced cellular toxicity and the optimum amount of methotrexate-BSA (2.83 mM) was 500 μl. Uptake of S-AuNPs was enhanced by folate conjugation that binds to folate receptors overexpressed by MDA-MB-231 and the optimum uptake was at 500 μl of folic acid-BSA (2.83 mM). TGF-β1 antibody on S-AuNP reduced extracellular TGF-β1 of cancer cells by 30%. Due to their efficacy and tunable properties, we anticipate numerous clinical applications of multifunctional gold nanospheres in treating breast cancer.
authors.affiliation: Department of Biomedical Engineering, Khalifa University of Science, Technology, and Research, PO Box 127788, Abu Dhabi, United Arab Emirates.
authors.forename: Nahla
authors.initials: N
authors.lastname: Rizk
authors.forename: Nicolas
authors.initials: N
authors.lastname: Christoforou
authors.forename: Sungmun
authors.initials: S
authors.lastname: Lee
mesh_terms: D000906:Antibodies / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005492:Folic Acid / Q000737:chemistry / Q000494:pharmacology*; D006046:Gold / Q000737:chemistry*; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry; D008727:Methotrexate / Q000737:chemistry / Q000494:pharmacology; D010316:Particle Size; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D006046:Gold; D005492:Folic Acid; D008727:Methotrexate