Combination Therapy of NSCLC Using Hsp90 Inhibitor and Doxorubicin Carrying Functional Nanoceria.
Shoukath SulthanaTuhina BanerjeeJyothi KalluSudershini Reddy VuppalaBlaze HeckertShuguftha NazTyler ShelbyOlivia YambemSantimukul SantraPublished in: Molecular pharmaceutics (2017)
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.
Keyphrases
- combination therapy
- small cell lung cancer
- cancer therapy
- advanced non small cell lung cancer
- drug delivery
- brain metastases
- oxide nanoparticles
- cell death
- heat shock protein
- heat stress
- squamous cell carcinoma
- high throughput
- epidermal growth factor receptor
- heat shock
- emergency department
- risk assessment
- reactive oxygen species
- papillary thyroid
- gold nanoparticles
- smoking cessation
- signaling pathway
- drug induced
- single cell
- squamous cell
- adverse drug
- highly efficient
- lymph node metastasis
- cell proliferation
- cell cycle arrest
- pi k akt