Bioactive glasses as potential radioisotope vectors for in situ cancer therapy: investigating the structural effects of yttrium.

The incorporation of yttrium in bioactive glasses (BGs) could lead to a new generation of radionuclide vectors for cancer therapy, with high biocompatibility, controlled biodegradability and the ability to enhance the growth of new healthy tissues after the treatment with radionuclides. It is essential to assess whether and to what extent yttrium incorporation affects the favourable properties of the BG matrix: ideally, one would like to combine the high surface reactivity typical of BGs with a slow release of radioactive yttrium. Molecular Dynamics simulations show that, compared to a BG composition with the same silica fraction, incorporation of yttrium results in two opposing effects on the glass durability: a more fragmented silicate network (leading to lower durability) and a stronger yttrium-mediated association between separate silicate fragments (leading to higher durability). The simulations also highlight a high site-selectivity and some clustering of yttrium cations, which are likely linked to the observed slow rate of yttrium released from related Y-BG compositions. Optimisation of yttrium BG compositions for radiotherapy applications thus depends on the delicate balance between these effects.

[1]  G. N. Greaves,et al.  EXAFS and the structure of glass , 1985 .

[2]  A. Cormack,et al.  Structural differences and phase separation in alkali silicate glasses , 1991 .

[3]  Z. Strnad.  Role of the glass phase in bioactive glass-ceramics. , 1992, Biomaterials.

[4]  Chikara Ohtsuki,et al.  Mechanism of apatite formation on CaOSiO2P2O5 glasses in a simulated body fluid , 1992 .

[5]  D. Day,et al.  Chemical durability of Y2O3-Al2O3-SiO2 glasses for the in vivo delivery of beta radiation. , 1993, Journal of biomedical materials research.

[6]  W Smith,et al.  DL_POLY_2.0: a general-purpose parallel molecular dynamics simulation package. , 1996, Journal of molecular graphics.

[7]  Chung-Cherng Lin,et al.  Structure and dissolution of CaO-ZrO2-TiO2-Al2O3-B2O3-SiO2 glass (II) , 1997 .

[8]  W. Lau,et al.  Internal radiation therapy for patients with primary or metastatic hepatic cancer , 1998, Cancer.

[9]  Walter Kob,et al.  Channel diffusion of sodium in a silicate glass , 2001 .

[10]  P. McMillan,et al.  A neutron diffraction study of yttrium- and lanthanum-aluminate glasses , 2002 .

[11]  J. Knowles.  Phosphate based glasses for biomedical applications , 2003 .

[12]  Julian D. Gale,et al.  The General Utility Lattice Program (GULP) , 2003 .

[13]  Jincheng Du,et al.  Sodium ion migration mechanisms in silicate glasses probed by molecular dynamics simulations , 2003 .

[14]  T. Campos,et al.  Structure and dosimetric analysis of biodegradable glasses for prostate cancer treatment. , 2003, Artificial organs.

[15]  A. Priven.  General method for calculating the properties of oxide glasses and glass forming melts from their composition and temperature , 2004 .

[16]  N. H. Leeuw,et al.  Shell-model molecular dynamics calculations of modified silicate glasses , 2006 .

[17]  N. D. de Leeuw,et al.  Ab initio molecular dynamics study of 45S5 bioactive silicate glass. , 2006, The journal of physical chemistry. B.

[18]  M. Hupa,et al.  Study of yttrium containing bioactive glasses behaviour in simulated body fluid , 2006, Journal of materials science. Materials in medicine.

[19]  G. Mountjoy,et al.  A molecular dynamics study of the atomic structure of (CaO)x(SiO2)1-x glasses. , 2006, The journal of physical chemistry. B.

[20]  N. H. Leeuw,et al.  The structure of bioactive silicate glasses : New insight from molecular dynamics simulations , 2007 .

[21]  A. Tilocca,et al.  Structural effects of phosphorus inclusion in bioactive silicate glasses. , 2007, The journal of physical chemistry. B.

[22]  N. D. de Leeuw,et al.  The formation of nanoscale structures in soluble phosphosilicate glasses for biomedical applications: MD simulations. , 2007, Faraday discussions.

[23]  M. Hupa,et al.  The behaviour of selected yttrium containing bioactive glass microspheres in simulated body environments , 2008, Journal of materials science. Materials in medicine.

[24]  A. Tilocca.  Short- and medium-range structure of multicomponent bioactive glasses and melts: An assessment of the performances of shell-model and rigid-ion potentials. , 2008, The Journal of chemical physics.

[25]  M. Menziani,et al.  Computational Insight into the Effect of CaO/MgO Substitution on the Structural Properties of Phospho-Silicate Bioactive Glasses , 2009 .

[26]  A. Tilocca.  Structural models of bioactive glasses from molecular dynamics simulations , 2009, Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[27]  Jincheng Du,et al.  A molecular dynamics simulation interpretation of neutron and x-ray diffraction measurements on single phase Y2O3–Al2O3 glasses , 2009, Journal of physics. Condensed matter : an Institute of Physics journal.

[28]  Jincheng Du.  Molecular Dynamics Simulations of the Structure and Properties of Low Silica Yttrium Aluminosilicate Glasses , 2009 .

[29]  Julian R. Jones,et al.  Differentiation of fetal osteoblasts and formation of mineralized bone nodules by 45S5 Bioglass conditioned medium in the absence of osteogenic supplements. , 2009, Biomaterials.

[30]  A. Tilocca.  Models of structure, dynamics and reactivity of bioglasses: a review , 2010 .

[31]  Antonio Tilocca,et al.  Short‐Range Structure of Yttrium Alumino‐Silicate Glass for Cancer Radiotherapy: Car–Parrinello Molecular Dynamics Simulations , 2010 .

[32]  A. Tilocca.  Sodium migration pathways in multicomponent silicate glasses: Car-Parrinello molecular dynamics simulations. , 2010, The Journal of chemical physics.

[33]  A. Tilocca,et al.  Aluminosilicate Glasses As Yttrium Vectors for in situ Radiotherapy: Understanding Composition-Durability Effects through Molecular Dynamics Simulations , 2010 .

[34]  Delbert E. Day,et al.  Glass and Medicine , 2010 .

[35]  R. Hill,et al.  Influence of strontium and the importance of glass chemistry and structure when designing bioactive glasses for bone regeneration. , 2010, Acta biomaterialia.

[36]  M. Menziani,et al.  Fluorine environment in bioactive glasses: ab initio molecular dynamics simulations. , 2011, The journal of physical chemistry. B.