羟基磷灰石纳米颗粒的体外和体内抗黑色素瘤作用：材料因素的影响。
The in vitro and in vivo anti-melanoma effects of hydroxyapatite nanoparticles: influences of material factors.
机构信息
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China,
Department of Dermatology, West China Hospital of Sichuan University, Chengdu 610041, China.
出版信息
Int J Nanomedicine. 2019 Feb 15;14:1177-1191. doi: 10.2147/IJN.S184792. eCollection 2019.
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.
背景
黑色素瘤的治疗是一个具有挑战性的临床问题，值得探索一些新的策略。
目的
本研究旨在探讨羟基磷灰石纳米粒子（HANPs）的体外和体内抗黑色素瘤作用，并探讨相关的材料因素。
材料与方法
采用湿化学法结合聚合物模板和适当的后处理，制备了 5 种 HANPs，即 HA-A、HA-B、HA-C、HA-D 和 HA-E。通过细胞计数试剂盒-8 分析、细胞核形态观察、流式细胞仪和 PCR 分析，评估了所制备的 5 种 HANPs 对 A375 黑色素瘤细胞活力的抑制作用和诱导细胞凋亡的作用。在裸鼠肿瘤模型中研究了 HANPs 的体内抗黑色素瘤作用。
结果
5 种 HANPs 具有不同的物理化学性质，包括形态、大小、比表面积（SSA）、结晶度等。通过体外细胞研究发现，材料因素在 HANPs 的抗黑色素瘤作用中起着重要作用。在所制备的 5 种 HANPs 中，颗粒状、较小尺寸、较高 SSA 和较低结晶度的 HA-A 对抑制 A375 细胞活力的效果最佳。在 200μg/ml 浓度下，HA-A 在第 3 天导致细胞活力最低（34.90%）。所有 HANPs 均可诱导 A375 细胞凋亡，在第 3 天，细胞凋亡率相对较高的是 HA-A（20.10%）和 HA-B（19.41%）。然而，所有 HANPs 对正常人表皮成纤维细胞的活力均无抑制作用。初步体内评价表明，HA-A 和 HA-C 均可显著延迟黑色素瘤组织的形成和生长速度。可能是 HA-A 对抑制黑色素瘤组织生长的效果优于 HA-C。HA-A 对肿瘤组织生长的抑制率在第 23 天达到 49.1%。
结论
本研究证实了 HANPs 的抗黑色素瘤作用，为黑色素瘤的临床治疗提供了新的思路。
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