sta-9090 and ceric-oxide

Topics: A549 Cells; Animals; Antineoplastic Agents; Antioxidants; Carcinoma, Non-Small-Cell Lung; Cerium; CHO Cells; Combined Modality Therapy; Cricetinae; Cricetulus; Glycolipids; Histone Deacetylase Inhibitors; HSP90 Heat-Shock Proteins; Humans; Lung Neoplasms; Triazoles

K-RAS driven non-small-cell lung cancer (NSCLC) represents a major cause of death among smokers. Recently, nanotechnology has introduced novel avenues for the diagnosis and personalized treatment options for cancer. Herein, we report a novel, multifunctional nanoceria platform loaded with a unique combination of two therapeutic drugs, doxorubicin (Doxo) and Hsp90 inhibitor ganetespib (GT), for the diagnosis and effective treatment of NSCLC. We hypothesize that the use of ganetespib synergizes and accelerates the therapeutic efficacy of Doxo via ROS production, while minimizing the potential cardiotoxicity of doxorubicin drug. Polyacrylic acid (PAA)-coated cerium oxide nanoparticles (PNC) were fabricated for the targeted combination therapy of lung cancers. Using "click" chemistry, the surface carboxylic acid groups of nanoceria were decorated with folic acid to target folate-receptor-overexpressing NSCLC. As a result of combination therapy, results showed more than 80% of NSCLC death within 48 h of incubation. These synergistic therapeutic effects were assessed via enhanced ROS, cytotoxicity, apoptosis, and migration assays. Overall, these results indicated that the targeted codelivery of Doxo and GT using nanoceria may offer an alternative combination therapy option for the treatment of undruggable NSCLC.

Topics: A549 Cells; Acrylic Resins; Animals; Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cerium; Combined Modality Therapy; Doxorubicin; Drug Carriers; Folic Acid; HSP90 Heat-Shock Proteins; Humans; Lung Neoplasms; Nanoparticles; Rats; Reactive Oxygen Species; Triazoles