Influences of material factors on the anti-melanoma effects of hydroxyapatite nanoparticles

摘要

Local tumor recurrence after melanoma resection is a great challenge of clinical treatment. Hydroxyapatite nanoparticles (HANPs) has been confirmed to have the ability to inhibit the proliferation of some tumor cells selectively in many previous studies. However, the correlation between the material factors of HANPs and the inhibitory proliferation or apoptosis of tumor cells need be further investigated. In the present study, we synthesized five hydroxyapatite nanoparticles (HANPs) with different physicochemical properties including morphology, size, specific surface area (SSA), crystallinity and so on by a wet chemical method combined with polymer template and appropriate post-treatments (Table 1). A375 melanoma cells and normal fibroblasts were used for co-culture with the various HANPs. The selective effect of HANPs on inhibiting the proliferation of A375 cells and inducing the apoptosis of the cells was evaluated by CCK-8 analysis, cell nucleus morphology observation, flow cytometer and PCR analysis. The results showed that the material factors played important roles in the anti-melanoma effect of HANPs. Among the as-prepared five HANPs, HA-A with granular shape, smaller size, higher SSA and lower crystallinity exhibited the strongest anti-melanoma effect. At the concentration of 200 μg/mL, HA-A obtained the highest proliferation inhibition ratio (65.1%) and apoptosis ratio (20.1%) of A375 cells after culturing for 3 days. Furthermore, an in vivo anti-melanoma evaluation was performed in a nude mice model. The mixture of the A375 cell suspension and HANPs was subcutaneously injected into the left side of the nude mouse, and the tumor formation and growth were observed and recorded. The results showed that HANPs significantly delayed the formation and growth speed of melanoma tissue, compared with the control group (without use of HANPs). At 23 days, the inhibition ratios of HA-A and HA-C for tumor tissue growth were 49.1% and 34.0%, respectively.The current study confirmed the anti-melanoma effect of HANPs and provided a new idea for the clinical treatment of melanoma.