<p>The in vitro and in vivo anti-melanoma effects of hydroxyapatite nanoparticles: influences of material factors</p>

Abstract

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.

<p>Nano-Hydroxyapatite Coating Promotes Porous Calcium Phosphate Ceramic-Induced Osteogenesis Via BMP/Smad Signaling Pathway</p>

“…These findings suggest that nHA not only induces osteogenesis to repair hard tissue injury but also promotes selective apoptosis of tumor cells. Thus, nHA has emerged as an ideal candidate for biomedical applications 18,19. However, it is difficult to endow CaP ceramics with both an interconnected porous structure and a bioactive nanostructured surface, as grains grow rapidly and pores collapse easily during the sintering process 1.…”

The Morphology of Hydroxyapatite Nanoparticles Regulates Cargo Recognition in Clathrin-Mediated Endocytosis

“…Therefore, the HAp-S with the diameter of 1.926 nm was used in the following calculations. On the other hand, changes of the nanoparticles’ geometrical parameters, such as the Ca:P ratio or the aspect ratio, may lead to variable net-charge and the electrostatic potential surface ( Supplementary Figure S1 ), though it was reported that the zeta potentials of HAp nanoparticles of various shape that have been characterized in experiments are all negative ( Wu et al, 2019 ); besides, changes in the size may also lead to a change in the geometric matching of the interface between the two. Therefore, we will focus on the interactions between the fixed-size nanoparticles ( Figure 1C,D ) and the protein in this work.…”

“…Hence, HAp-S leads to a more significant conformational change on AP2-μ2 than that of HAp-N. In literature, it was reported that the sphere-shaped HAp nanoparticles effectively inhibited the growth of A375 melanoma cells (34.90% viability); in contrast, the rod or needle-like HAp nanoparticles moderately affected the viabilities of melanoma cells (60.43%–74.90%) ( Wu et al, 2019 ). Presumably, HAp-S is likely to facilitate its transportation in the cellular environment by shifting AP2-μ2 to a locked conformation, and therefore resulting in a more profound tumor-suppressive effect.…”

“…We previously characterized the HAp nanoparticles and their inhibitory activities against tumor cells or promoting activities on normal tissue cells, and elucidated the downstream signaling pathways evoked by HAp-internalization and others ( Chen et al, 2013 ; Zhao et al, 2017 ; Wang et al, 2018a ; Zhang et al, 2019a ; Liu et al, 2019 ; Wang et al, 2019 ; Wu et al, 2019 ; Li et al, 2020 ). If the cells were pretreated with chlorpromazine (clathrin-pathway inhibitor) ( Shi et al, 2017 ) or NaN 3 (ATP inhibitor), ( Ryan et al, 2015 ) the uptake of HAp were significantly prohibited, indicating clathrin-mediated and ATP-dependent endocytosis for HAp nanoparticles.…”

Tuning Coordination Modes and Nucleation of Calcium Phosphate with Oligomeric Lactic Acid and pH Values: Theoretical and Experimental Study

“…Although the zeta potential values measured by different research groups may be different from each other, the experimental data of various nanoparticles collected in Table 1 could still give some general trends, especially for the potential of binding with the biological moelcules. As shown in Table 1, the HA nanoparticles with different morphologies, 14 Ag@HA, 30 F-Cl@HA, 31 and Au/Ag@ HA, 35 had negative zeta potentials, some of which were found to be efficiently taken up by A375 cells and MG-63 cells. The HA particles with several kinds of oxygencontaining addtives, such as, citric acid@HA, 32 oxalic acid@HA 33 and malic acid@HA 34 also exhibited negative zeta potentials, whose values were dependent on the pH values (Table 1), Similar to HA nanoparticles, some other nanoparticles including Au/Ag nanoparticles, 35 cerium oxide nanoparticles 76 and iron oxide nanoparticles 29 with negative zeta potentials were able to effectively absorbed on MG-63, A549, and HeLa cells.…”