A systematic assessment of hydroxyapatite nanoparticles used in the treatment of melanoma

Abstract

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.

Osteoporotic bone recovery by a bamboo-structured bioceramic with controlled release of hydroxyapatite nanoparticles

“…The biological effect of nHA has been reported to be related to its concentration and the cell type that interacts with it. In the last decade, nHA was found to be capable of inhibiting proliferation and inducing apoptosis in various cancer cells, including osteosarcoma cells, breast cancer cells, gastric cancer cells, and melanoma, but also promoting the proliferation and mineralization of osteoblastic cell lines [ [24] , [25] , [26] ]. Our group first discovered that low-crystallinity nHA with a size of 40–60 nm could promote the bone-forming ability of diseased osteoblasts isolated from osteoporotic bone explants [ 27 ].…”

Anti-melanoma effect and action mechanism of a novel chitosan-based composite hydrogel containing hydroxyapatite nanoparticles

“…SK-MEL-28 and A375 human malignant melanoma cell line was performed as previously described [ 27 ]. The human keratinocytes (HaCaT) cell line was supplied by Guangzhou Cellcook Biotech Co., Ltd (China).…”

“…Our research group has indicated that rod-like HANPs had the most prominent suppressive effect. They suppressed melanoma tumor proliferation both in vitro and in vivo and enhanced the viability of normal skin fibroblasts, indicating a potential for their use in the post-operative treatment of CMM [ 27 ]. However, whether the HANPs induce apoptosis and corresponding microenvironment alterations, along with the possible underlying mechanisms, require further investigation.…”

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

“…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.…”