Different Inhibitory Effect and Mechanism of Hydroxyapatite Nanoparticles on Normal Cells and Cancer Cells In Vitro and In Vivo

Abstract

Hydroxyapatite (HAP), similar to inorganic phase in bones, shows good biocompatibility and bioactivity as bone defect repairing material. Recently, nanoscaled HAP shows the special properties differing from bulk HAP in physics, chemistry and biology. This paper demonstrates that HAP nanoparticle (nHAP) possesses the ability for inhibiting cancer cell growth in vitro and in vivo. In vitro, after treatment with nHAP for 3 days, proliferation of human cancer cells are inhibited by more than 65% and by less than 30% for human normal cells. In vivo, injection of nHAP in transplanted tumor results in significant reduction (about 50%) of tumor size. The anticancer effect of nHAP is mainly attributed to high amount by endocytosis in cancer cells and inhibition on protein synthesis in cells. The abundant nHAP internalized in cancer cells around endoplasmic reticulum may inhibit the protein synthesis by decreasing the binding of mRNA to ribosome due to its high adsorption capacity for ribosome and arrest cell cycle in G0/G1 phase. nHAP shows no ROS-involved cytotoxicity and low cytotoxicity to normal cells. These results strongly suggest that nHAP can inhibit cancer cell proliferation and have a potential application in cancer treatment.

Hydroxyapatite as a Vehicle for the Selective Effect of Superparamagnetic Iron Oxide Nanoparticles against Human Glioblastoma Cells

“…48 Gastric cancer, liver cancer, and osteosarcomas cell lines also experienced a greater degree of proliferation inhibition than did the primary hepatocytes, lung fibroblasts, and keratinocytes. 49 Effects on lung cells challenged with HAP were similarly selective: toxic to alveolar adenocarcinoma A549 cells and harmless to normal bronchial epithelial 16HBE cells. 50 However, no cytotoxic effects of pure HAP on any glioblastoma cells have been reported previously.…”

Selective anticancer activity of hydroxyapatite/chitosan-poly(d,l)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor

“…For example, HAp nanoparticles, albeit doped with selenite ions and injected into the bloodstream, extended the lifetime of mice with hepatocellular carcinoma [34]. Also, a direct injection of HAp nanoparticles into a transplanted tumor formed by Bel-7402 human hepatocarcinoma cells in nude mice led to a 50 % reduction in the tumor size [35]. On the other hand, the antiproliferative activity of HAp was twice more intense for cancer cells than for the normal ones, both in vitro and in vivo [35].…”

Biodegradable and Biocompatible Systems Based on Hydroxyapatite Nanoparticles

“…Recent works have indicated that high concentration of HAp nanoparticles may show an antiproliferative and proapoptotic activity on cancer cells [155,156]. Specifically, adverse effects on the metabolic viability of several types of cancer cells (e.g., hepatoma, colon cancer, osteosarcoma, and melanoma) have been detected [157,158].…”