Preparation, characterization, in vitro and in vivo anti-tumor effect of thalidomide nanoparticles on lung cancer.

ABSTRACT

INTRODUCTION: Thalidomide (THA) is an angiogenesis inhibitor and an efficient inhibitor of the tumor necrosis factor-α (TNF-α). However, the clinical application of THA has been limited due to hydrophobicity of the compound. MATERIALS AND METHODS: To increase the water solubility of THA and in order to evaluate the anticancer abilities of this material on human lung carcinoma, methoxy poly(ethylene glycol)-poly(ε-caprolactone) nanoparticles loaded with THA (THA-NPs) were prepared. The synthesis of THA-NPs was carried out via a dialysis method with relative satisfactory encapsulation efficiency, loading capacity, size distribution, and zeta potential. RESULTS: A cytotoxicity assay demonstrated that THA-NPs inhibited the growth of cells in a dose-dependent manner. The evaluation of anti-tumor activity in vivo showed that THA-NPs could inhibit tumor growth and prolong the survival rate of tumor-bearing mice. Immunohistochemical analysis indicated that THA-NPs inhibited cell proliferation (Ki-67 positive rate, 32.8%±4.2%, P<0.01), and resulted in a decreased rate of the tumor tissue microvessel density (3.87%±0.77%, P<0.01), VEGF (26.67%±4.02%, P<0.01), and TNF-α (75.21±6.85 ng/mL, P<0.01). CONCLUSION: In general, the drug delivery system reported herein may shed light on future targeted therapy in lung cancer treatment.