With both nanovectors, toxic effects affecting the mice weight or inducing deaths were not found. Finally, the histological examination of some vital organs such as liver, kidney, and spleen did not find any changes in terms of necrotic effects or modifications in the inflammatory MLN0128 infiltrate [41]. The

ability of BPs to bind metal ions was used to prepare BP-complexing superparamagnetic iron oxide nanocrystals with theranostic purposes [44–46]. In a first study, a 5-hydroxy-5, 5-bis(phosphono) pentanoic acid was used, while in the following works more powerful BPs, such as ALE and ZOL, were used. Amino fluorescein or rhodamine were covalently coupled with the nanocrystal, thus allowing Inhibitors,research,lifescience,medical to visualize an efficient uptake Inhibitors,research,lifescience,medical of the nanovector into two different cell lines [44, 104]. However, cell viability assays demonstrated that ZOL alone had an IC50 at 48h that was 1 order of magnitude lower than with γFe2O3-ZOL nanocrystals. According to the authors, cell proliferation decreases to 75% under an applied magnetic field, compared to 40% without magnetic field [45]. γFe2O3-ALE NPs were investigated on different cell lines; however, a clear advantage of the NPs was found only on breast cancer cell [104]. These NPs were also investigated in vivo in an experimental model of breast cancer [104]. In

Inhibitors,research,lifescience,medical this study, tumour growth in animals treated with free ALE and γFe2O3-ALE NPs was not significantly different than in control group. NPs used in combination with a magnetic Inhibitors,research,lifescience,medical field significantly inhibited tumour growth by about 60% after 5 weeks, with all mice treated that were alive 5 weeks after treatment and did not present significant loss of body weight. However, the lack of control Inhibitors,research,lifescience,medical experiments with γFe2O3 NPs (NPs without ALE) hampers to affirm that ALE could be responsible for the antitumor affect, while the physical effect of NPs under the magnetic field could be the main

responsible of anticancer effect described by the authors. 8. Nanotechnology and BPs: Targeting of Bone Tumors Bone metastasis, Tryptophan synthase especially originating by breast and prostate cancer, are the most frequent form of skeletal neoplasia. In the majority of patients, treatments of bone metastasis are palliative, being aimed to relieve pain, improve function, and prevent complications such as spinal cord compression and pathological fracture. The development of anticancer therapies with high affinity for bone and reduced distribution to other sites is certainly attractive. To this aim, nanovectors targeting hydroxyapatite have been proposed. Hydroxyapatite (Ca10(PO4)6(OH)2) is the major inorganic mineral phase present in bone and teeth and not found in other tissues under normal circumstances. Thus, the use of nanocarriers conjugated to BPs that are characterized by high affinity for hydroxyapatite have been proposed.