Hyperthermia effect and antibacterial efficacy of Fe³⁺/Co²⁺ co‐substitutions in β‐Ca₃(PO₄)₂ for bone cancer and defect therapy

Abstract

The combined effect of cobalt and iron substitutions in β-Ca (PO ) as a potent material for application in hyperthermia and as a bone substitute is presented. Structural analysis reveals the preferential accommodation of Co and Fe at the Ca (5) sites of β-Ca (PO ) until the limit of ∼10 mol % and, thereafter, prefer Ca (4) lattice sites. Occupancy of both the Co and Fe ions induces a significant contraction of the β-Ca (PO ) unit cell. The Co /Fe co-substitutions in β-Ca (PO ) display magnetic characteristics that enhances hyperthermia effect. In addition, the presence of Co in β-Ca (PO ) enunciates pronounced antibacterial efficacy against tested microorganisms. Nevertheless, the enhanced level of Co in β-Ca (PO ) results to induce significant toxicity. The biocompatibility of the synthesized thermoseeds is verified from the hemolytic tests and cytotoxicity test performed on human sarcoma cell line MG-63. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1317-1328, 2018.

Progress of biomaterials for bone tumor therapy

“…57 Another study also found that the accommodation of both Co 2þ and Fe 3þ in b-tricalcium phosphate could not only improve the hyperthermal effects, but also induce obvious antibacterial efficacy. 58 In addition, there is great potential for hydroxyapatite modified with Fe 3 O 4 for bone tumor treatment. 59 Collagen/hydroxyapatite with 1 or 2% magnetite content produced insufficient hyperthermia, while composite scaffolds with a magnetite content of 5% could act as regenerative scaffolds with hypothermic antitumoral effects.…”

Ionic Substitutions in Non-Apatitic Calcium Phosphates

“…Ionic substitution in both α and βTCP is currently being investigated. A solid-state reaction, as well as the heat treatment of already precipitated powders, are commonly applied to synthesize these materials [ 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 ]. It is worth underlining that there are two main directions in ionic modification of α and βTCP.…”

“…It is not only magnesium that is being introduced into the βTCP crystal lattice. In the literature, following examples of other ionic modifications can be found: sodium [ 127 , 143 ], potassium [ 128 ], silver [ 135 ], manganese [ 132 ], silicon [ 111 , 133 ], strontium [ 107 , 112 , 113 , 114 ], copper [ 136 ], cobalt [ 137 ], aluminium [ 146 ], iron [ 139 , 140 , 141 ], lantanium [ 131 ], and rare earth elements [ 145 ].…”

“…Recent works also focused on iron-doped βTCP [ 139 , 140 , 141 ]. Considering the fact that CPCs substituted with magnetic ions (i.e., Fe 3+ ) exhibit ferromagnetic properties, they may be used as heat mediators in hyperthermia treatment of tumors, drug delivery systems or biomaterials for magnetic resonance imaging (MRI) [ 141 ].…”

“…Detailed studies on ferric doping mechanism was presented in [ 141 ]. Hyperthermia effect was investigated on Fe 3+ /Ni 2+ co-substituted βTCP [ 139 ]. High nickel content exhibited significant cytotoxicity.…”