Hydroxyapatite (HA) has been widely applied in bone repair because of its superior biocompatibility. Recently, a proliferation-suppressive effect of HA nanoparticles (n-HA) against various cancer cells was reported. This study was aimed at assessing the translational value of n-HA both as a bone-regenerating material and as an antitumor agent. Inhibition of tumor growth, prevention of metastasis, and enhancement of the survival rate of tumor-bearing rabbits treated with n-HA were demonstrated. Activated mitochondrial-dependent apoptosis in vivo was confirmed, and we observed that a stimulated immune response was involved in the n-HA–induced antitumor effect. A porous titanium scaffold loaded with n-HA was fabricated and implanted into a critical-sized segmental bone defect in a rabbit tumor model. The n-HA–releasing scaffold not only showed a prominent effect in suppressing tumor growth and osteolytic lesion but also promoted bone regeneration. These findings provide a rationale for using n-HA in tumor-associated bone segmental defects.

Background Treatment for melanoma is a challenging clinical problem, and some new strategies are worth exploring. Purpose The objective of this study was to investigate the in vitro and in vivo anti-melanoma effects of hydroxyapatite nanoparticles (HANPs) and discuss the involved material factors. Materials and methods Five types of HANPs, ie, HA-A, HA-B, HA-C, HA-D, and HA-E, were prepared by wet chemical method combining with polymer template and appropriate post-treatments. The in vitro effects of the as-prepared five HANPs on inhibiting the viability of A375 melanoma cells and inducing the apoptosis of the cells were evaluated by Cell Counting Kit-8 analysis, cell nucleus morphology observation, flow cytometer, and PCR analysis. The in vivo anti-melanoma effects of HANPs were studied in the tumor model of nude mice. Results The five HANPs had different physicochemical properties, including morphology, size, specific surface area (SSA), crystallinity, and so on. By the in vitro cell study, it was found 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 best effect on inhibiting the viability of A375 cells. At the concentration of 200 μg/mL, HA-A resulted in the lowest cell viability (34.90%) at day 3. All the HANPs could induce the apoptosis of A375 cells, and the relatively higher apoptosis rates of the cells were found in HA-A (20.10%) and HA-B (19.41%) at day 3. However, all the HANPs showed no inhibitory effect on the viability of the normal human epidermal fibroblasts. The preliminary in vivo evaluation showed that both HA-A and HA-C could delay the formation and growth speed of melanoma tissue significantly. Likely, HA-A exhibited better effect on inhibiting the growth of melanoma tissue than HA-C. The inhibition rate of HA-A for tumor tissue growth reached 49.1% at day 23. Conclusion The current study confirmed the anti-melanoma effect of HANPs and provided a new idea for the clinical treatment of melanoma.

Melanoma is a highly malignant skin tumor which is prone to recurrence and metastasis. Hydroxyapatite nanoparticles (nHAPs) were reported to possess a suppressive effect on proliferation of various tumor cells in vitro. This study aimed to assess in vitro and in vivo anti-tumor ability and biosafety of the nHAPs used in the treatment of melanoma. Three types of nHAPs with different morphology and crystallinity were synthesized. In vitro cell viability and proliferation studies demonstrated that all three types of nHAPs can inhibit viability and proliferation of A375 and SK-MEL-28 melanoma cells in a concentration-dependent manner. In addition, the rod-shape nHAPs with a crystallinity of 45.60% had the most prominent suppressive effect on the two melanoma cells tested. An important positive regulator of G1/S phase transition in cell cycle, Cyclin D1 protein, was reduced by nHAPs treatment in vivo. We further discovered that the migration ability of the nHAPs treated melanoma cells was greatly decreased. RNA sequencing result revealed that melanoma metastasis related genes were down-regulated by nHAPs, including MMP2, MMP14, ITGA9, ITGB3, ITGB4 and S100B. High concentration of nHAPs treatment in melanoma-bearing nude mice showed a strong inhibitory effect on tumor size and weight. Most importantly, hemolysis, electrolyte disturbance or inflammation response was not discovered in the experimental animals from nHAPs treated groups. We proved that the nHAPs synthesized in the current study has a selective effect to suppress melanoma tumor proliferation and was safe with regard to normal cells and tissue.

Polyetheretherketone (PEEK) has been widely used in the fields of orthopedics and trauma, but weak osteointegration and bacterial infection affect its long-term stability and repair effects. Surface modification is an...

The clathrin-associated protein adaptin-2 (AP2) is a distinctive member of the hetero-tetrameric clathrin adaptor complex family. It plays a crucial role in many intracellular vesicle transport pathways. The hydroxyapatite (HAp) nanoparticles can enter cells through clathrin-dependent endocytosis, induce apoptosis, and ultimately inhibit tumor metastasis. Exploring the micro process of the binding of AP2 and HAp is of great significance for understanding the molecular mechanism of HAp’s anti-cancer ability. In this work, we used molecular modeling to study the binding of spherical, rod-shaped, and needle-shaped HAps toward AP2 protein at the atomic level and found that different nanoparticles’ morphology can determine their binding specificity through electrostatic interactions. Our results show that globular HAp significantly changes AP2 protein conformation, while needle-shaped HAP has more substantial binding energy with AP2. Therefore, this work offers a microscopic picture for cargo recognition in clathrin-mediated endocytosis, clarifies the design principles and possible mechanisms of high-efficiency nano-biomaterials, and provides a basis for their potential anti-tumor therapeutic effects.

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