Antitumor activity of intratracheal inhalation of temozolomide (TMZ) loaded into gold nanoparticles and/or liposomes against urethane-induced lung cancer in BALB/c mice

Abstract

The current study aimed to develop gold nanoparticles (GNPs) and liposome-embedded gold nanoparticles (LGNPs) as drug carriers for temozolomide (TMZ) and investigate the possible therapeutic effects of intratracheal inhalation of nanoformulation of TMZ-loaded gold nanoparticles (TGNPs) and liposome-embedded TGNPs (LTGNPs) against urethane-induced lung cancer in BALB/c mice. Physicochemical characters and zeta potential studies for gold nanoparticles (GNPs) and liposome-embedded gold nanoparticles (LGNPs) were performed. The current study was conducted by inducing lung cancer chemically via repeated exposure to urethane in BALB/C mice. GNPs and LGNPs were exhibited in uniform spherical shape with adequate dispersion stability. GNPs and LGNPs showed no significant changes in comparison to control group with high safety profile, while TGNPs and LTGNPs succeed to improve all biochemical data and histological patterns. GNPs and LGNPs are promising drug carriers and succeeded in the delivery of small and efficient dose of temozolomide in treatment lung cancer. Antitumor activity was pronounced in animal-treated LTGNPs, these effects may be due to synergistic effects resulted from combination of temozolomide and gold nanoparticles and liposomes that may improve the drug distribution and penetration.

Keywords: Intratracheal inhalation; chemotherapy; gold nanoparticles; liposomes; temozolomide.

Figure 1.

Physicochemical characteristics of the electron microscopic images of blank GNPs and TGNPs (A and B, respectively) (50×); C and D microscopic images of LGNPs and LTGNPs under the electron microscope, respectively (c and d) (200×).

Figure 2.

Effect of TMZ nanoparticles on serum cytokeratin 19 fragments (CYFRA 21-1) level in BALB/C mice treated with urethane-induced lung cancer. Within each bar, means superscript with * significantly different from normal control and ^asignificantly different from lung cancer control (p < 0.05).

Figure 3.

Effect of TMZ nanoparticles on serum insulin-like growth factor-1 (IGF-1) level in BALB/C mice treated with urethane-induced lung cancer. Within each bar, means superscript with * significantly different from normal control and ^asignificantly different from lung cancer control (p < 0.05).

Figure 4.

A photomicrograph of lung sections of control group (A) showing normal epithelization of bronchi and bronchioles with normal alveoli and normal configuration of thymus; (B) urethane-treated mice exhibiting foccal aggregation of neoplastic epithelial cells around the bronchioles and marked pleomorphic and advanced mitotic activities; (C) GNPs-treated mice showing few peribronchial proliferations of fibroblast cells and hemolysis of blood vessels; (D) Mice treated with LGNPs showing few peribronchial proliferations of fibroblast cells together with few lymphocytes and macrophages and hemolysis of blood vessels; (E) treated with Urethane + GNPs demonstrating few peribronchial and perivascular aggregation of neoplastic cells and severe proliferation of pneumocytes and occlusion of air alveoli and slightly hemolysis of blood vessels; (F) lung sections from mice treated with urethane + LGNPs exhibiting group of parabronchial aggregation of neoplastic cells with marked pleomorphic and advanced mitotic activities and notice congestion and edema in the alveoli; (G) lung section from mice animals treated with Urethane + TGNPs showing hyperplasia of bronchial epithelial cells and severe hemolysis of blood vessels with mild proliferation of pneumocytes among alveoli; (H) lung section from animal treated with urethane + LTGNPs display paravascular aggregation of lymphocytes and few fibroblast cells and hyperplasia of bronchial epithelial cells and marked alveolar edema with hemolysis in blood vessels. (H&E X 200).