In vivo antitumor effect of endostatin-loaded chitosan nanoparticles combined with paclitaxel on Lewis lung carcinoma

Abstract

The purpose of this study was to prepare endostatin-loaded chitosan nanoparticles (ES-NPs) and evaluate their antitumor effect when combined with paclitaxel (PTX) on Lewis lung carcinoma (LLC) mouse xenografts. ES-NPs were prepared by ionic cross-linking. Characterization of the ES-NPs included size distribution, drug-loading efficiency (DL), and encapsulation efficiency (EE). An in vitro release test was also used to determine the release behavior of the ES-NPs. A subcutaneous LC xenograft model of C57BL/6J mice was established. The mice were randomly divided into six groups: control (0.9% NaCl), ES, PTX, ES-NPs, ES þ PTX, and ES-NPs þ PTX. The tumor volume was dynamically measured for the duration of the experiment. Immunohistochemistry was performed to determine the Ki-67 and microvascular density (MVD) in each group. Serum vascular endothelial growth factor (VEGF) and ES levels were determined by enzyme-linked immunosorbent assay (ELISA). ES-NPs were successfully synthesized and had suitable size distribution and high EE. The NPs were homogenously spherical and exhibited an ideal release profile in vitro. In vivo, tumor growth was significantly inhibited in the ES-NPs þ PTX group. The tumor inhibitory rate was significantly higher in the ES-NPs þ PTX group than in the other groups (p < .05). The results of the immunohistochemical assay and ELISA confirmed that ES-NPs combined with PTX had a strong antiangiogenic effect. ES-NPs can overcome the shortcomings of free ES, such as short retention time in circulation, which enhances the antitumor effect of ES. The antitumor effect was more pronounced when treatment included PTX and ES-loaded NPs.ARTICLE HISTORY

Synergistic combination therapy of lung cancer using paclitaxel- and triptolide-coloaded lipid&ndash;polymer hybrid nanoparticles

“…The lung tumor xenografts were randomly assigned to eight groups (n = 10 each): 0.9% saline control, P solution (10 mg/kg), T solution (6 mg/kg), P/T solution (5 mg/kg of PTX and 3 mg/kg of TL), blank LPNs, P-LPNs (10 mg/kg), T-LPNs (6 mg/kg), and P/T-LPNs (5 mg/kg of PTX and 3 mg/kg of TL) were administered intravenously every other day for 18 days. 37 Mice were sacrificed by cervical dislocation on day 20, and the tumor tissues were collected for further analysis. During the treatment, tumor size (length and width) was measured using calipers every 4 days.…”

Application of Light Scattering Techniques to Nanoparticle Characterization and Development

“…To confirm NP coating with both peptides, authors used DLS, evaluating afterwards the differences in activity (Lee et al, 2004 ). Also targeting tumors, iron oxide NPs coated with an heptapeptide that recognize fibrin-fibronectin complexes or chitosan NPs with antiangiogenic peptide endostatin (ES) improved anticancer activity by targeting the vascularization of the tumor (Agemy et al, 2010 ; Xie et al, 2017 ). Coating nanoparticle surfaces with two or more different peptides was also reported (Colombo et al, 2002 ; Marchiò et al, 2004 ).…”

A novel radio-sensitization method for lung cancer therapy: enhanced radiosensitization induced by antigens/antibodies reaction after targeting tumor hypoxia using Bifidobacterium

“…This vasculature can be characterized by disorganization, dilation, branching, shunts, and varied diameters that result in an inconsistent blood flow and hypoxic areas and regions of high acidity [35,36] . As previously reported, a lower MVD is related to slower tumor growth and improved biologic and clinical behavior [37][38][39][40] . Mice in the Ab+ Bi+ RT group showed the lowest expression of CD-31 and Ki-67 compared to mice in other groups.…”