Methods: In vitro, physicochemical properties of the Stattic-entrapped C-PLGA nanoparticles (S@C-PLGA) and Stattic-entrapped PLGA nanoparticles (S@PLGA, control) in terms of size, zeta potential, polydispersity index, drug loading, entrapment efficiency, Stattic release in different medium and cytotoxicity were firstly evaluated. The in vitro antimigration properties of the nanoparticles on breast cancer cell lines were then studied by Scratch assay and Transwell assay. Study on the in vivo antitumor efficacy and antimetastatic properties of S@C-PLGA compared to Stattic were then performed on 4T1 tumor bearing mice.
Results: The S@C-PLGA nanoparticles (141.8 ± 2.3 nm) was hemocompatible and exhibited low Stattic release (12%) in plasma. S@C-PLGA also exhibited enhanced in vitro anti-cell migration potency (by >10-fold in MDA-MB-231 and 5-fold in 4T1 cells) and in vivo tumor growth suppression (by 33.6%) in 4T1 murine metastatic mammary tumor bearing mice when compared to that of the Stattic-treated group. Interestingly, the number of lung and liver metastatic foci was found to reduce by 50% and 56.6%, respectively, and the average size of the lung metastatic foci was reduced by 75.4% in 4T1 tumor-bearing mice treated with S@C-PLGA compared to Stattic-treated group (p < 0.001).
Conclusion: These findings suggest the usage of C-PLGA nanocarrier to improve the delivery and efficacy of antimetastatic agents, such as Stattic, in cancer therapy.
MATERIALS AND METHODS: The cytotoxicity was studied by examining the hFOB cell response by MTT assessment. The cell morphology was evaluated by inverted microscopy and observed under scanning electronic microscopy (SEM).
RESULTS: MTT assay results displayed that the Cu content on the surface of Ti-6Al-7Nb alloys did not produce any cytotoxic effect on cell viability. The cell viability rate in all samples ranges from 97% to 126%, indicating that hFOB cells grew at a high proliferation rate. However, no significant differences in cell viability were observed between Ti and Ti Cu and between Ti HA and Ti Cu/HA groups. Microscopic examination demonstrated no difference in the cell morphology of hFOB among all samples. In addition, SEM observation indicated favorable adhesion and spreading of the cells on the coated and uncoated samples.
CONCLUSIONS: The surface modification of Ti-6Al-7Nb alloy with Cu, HA, and Cu/HA exhibits good cell biocompatibility, and the Cu has no influence on the cell proliferation and differentiation of hFOB.