title: Combination Therapy of NSCLC Using Hsp90 Inhibitor and Doxorubicin Carrying Functional Nanoceria.
abstract: 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.
authors.forename: Shoukath
authors.initials: S
authors.lastname: Sulthana
authors.forename: Tuhina
authors.initials: T
authors.lastname: Banerjee
authors.forename: Jyothi
authors.initials: J
authors.lastname: Kallu
authors.forename: Sudershini Reddy
authors.initials: SR
authors.lastname: Vuppala
authors.forename: Blaze
authors.initials: B
authors.lastname: Heckert
authors.forename: Shuguftha
authors.initials: S
authors.lastname: Naz
authors.forename: Tyler
authors.initials: T
authors.lastname: Shelby
authors.affiliation: Department of Neurology, College of Medicine, University of Tennessee Health Science Center , 855 Monroe Avenue, Memphis, Tennessee 38163, United States.
authors.forename: Olivia
authors.initials: O
authors.lastname: Yambem
authors.affiliation: Department of Chemistry, Kansas Polymer Research Center, Pittsburg State University , 1701 S. Broadway Street, Pittsburg, Kansas 66762, United States.
authors.forename: Santimukul
authors.identifier: 0000-0002-5047-5245
authors.initials: S
authors.lastname: Santra
mesh_terms: D000072283:A549 Cells; D000180:Acrylic Resins / Q000008:administration & dosage; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D002563:Cerium / Q000008:administration & dosage*; D003131:Combined Modality Therapy / Q000379:methods; D004317:Doxorubicin / Q000494:pharmacology*; D004337:Drug Carriers / Q000008:administration & dosage; D005492:Folic Acid / Q000008:administration & dosage; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D000180:Acrylic Resins; D004337:Drug Carriers; D018841:HSP90 Heat-Shock Proteins; D017382:Reactive Oxygen Species; C533237:STA 9090; D014230:Triazoles; D002563:Cerium; C006903:carbopol 940; C030583:ceric oxide; D004317:Doxorubicin; D005492:Folic Acid
keywords: Hsp90 inhibitor; NSCLC treatment; combination therapy; doxorubicin; drug delivery; nanoceria