As shown in Fig. 4c, CPT-TMC-treated tumors showed significantly more apoptotic cells (with green nuclei) than tumors from CPT, TMC or NS treated groups. The apoptosis index was significantly higher in CPT-TMC-treated group compared with the controls (**P < 0.01): Mean apoptotic index ± SD of tumor cells treated with CPT-TMC was 41.4 ± 2.8% when it was 34 ± 3.9%,

8.2 ± 2.2%, or 5.8 ± 1.6% in CPT, TMC, or NS treated group, respectively (Fig. 4d). These results suggested that the increased tumor cell apoptosis by CPT-TMC treatment in vivo may explain why tumor volumes shrinked. CPT-TMC inhibited intratumoral angiogenesis https://www.selleckchem.com/products/a-769662.html Anti-angiogenesis is a major anticancer mechanism. Therefore, MVD was evaluated in the tumors by counting the number of microvessels in sections stained with CD31 to further investigate the anti-angiogenic effect of CPT-TMC. CD31-positive single or a cluster Selleckchem Roscovitine of cells were counted as the microvessels (Fig. 4e). As shown in Fig. 4f, MVD reduced the most significantly in CPT-TMC-treated group (20.4 ± 2.9) compared with CPT (36.8 ± 2.5), TMC (58.8 ± 2.9) and NS treatments (61 ± 2; **P < 0.01). No significant difference was found between TMC group and NS group (P > 0.05). The inhibition of tumor neovascularization after CPT-TMC treatment may partially explain the apoptosis induction which subsequently

reduce tumor progression and finally prolong survival time. Discussion Nanoparticles may be defined as submicronic colloidal systems that are generally composed of polymers. In recent years, Orotidine 5′-phosphate decarboxylase nanoparticles have been explored with some success in maintaining or improving the anti-tumor activity of the anticancer agents. Nanoparticles can penetrate into the membrane cells and spread along the nerve synapses, blood vessels and lymphatic vessels, with the capacity of selectively accumulating in different cells and certain cell structures at the same time. The formulation of

nanoparticles and physicochemical parameters such as pH, surface charge are critical for drug delivery. The interaction of drug carrier systems with the biological environment is important for designing strategies: these systems should be independent in the environment and selective at the pharmacological site. If designed appropriately, nanoparticles may act as a powerful drug vehicle able to target tumor tissues or cells and prevent the drug from inactivation during its transportation. The selection of agents as drug delivery system is essential in the process of nanoparticle preparation for drug delivery system. Chitosan is renowned for its function of drug and gene delivery to cells and tissues [17, 18]. The medical materials made of chitosan, not only possess the characteristics of the general physicochemical polymer materials, such as mechanical stability and acceptability to sterilization, but also can be transformed into small molecular substances.