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Faculty of Pharmacy, University of Sydney, Sydney, New South Wales, Australia

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Ching-Yee Loo

Faculty of Pharmacy, University of Sydney, Sydney, New South Wales, Australia

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Alexander V Zavgorodniy

Faculty of Pharmacy, University of Sydney, Sydney, New South Wales, Australia

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Ramin Rohanizadeh

* Author for correspondence

Faculty of Pharmacy, University of Sydney, Sydney, New South Wales, Australia.

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Email the corresponding author at ramin.rohanizadeh@sydney.edu.au

Published Online:17 May 2012https://doi.org/10.4155/tde.12.39

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Abstract

The long-recognized promise of gene therapy to treat a broad range of currently incurable diseases remains largely unfulfilled, hindered by lack of a safe and efficient delivery vehicle. Hydroxyapatite nanoparticles are deemed a feasible candidate and possess many characteristics desired of an ideal gene vector. Current fabrication techniques can readily synthesize hydroxyapatite particles in the nanometer range; however, these particles suffer from extensive aggregation and heterogeneity, mainly in size, shape and surface charge, which render them inappropriate for gene-therapy application. There is thus a pertinent need to develop a method capable of fabricating homogenous and monodispersed hydroxyapatite nanoparticles in a rapid, efficient and cost-effective manner that can be easily upscaled. Cell transfection is impeded by several physical and biological barriers, with the vector’s properties highly determinant of its ability to overcome these barriers. Fine-tuning hydroxyapatite nanoparticles’ morphological and physicochemical properties, achievable through precise regulation of the reaction environment, can enhance transfection efficiencies of particles, in turn, generating safe and effective gene vectors.

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

References

1 Gorecki DC. Prospects and problems of gene therapy: an update. Exp. Opin. Emerg. Drugs6(2),187–198 (2001).
Medline CASGoogle Scholar
2 Edelstein ML, Abedi MR, Wixon J. Gene therapy clinical trials worldwide to 2007 – an update. J. Gene Med.9(10),833–842 (2007).
MedlineGoogle Scholar
3 Nishikawa M, Huang L. Nonviral vectors in the new millennium: delivery barriers in gene transfer. Hum. Gene Ther.12(8),861–870 (2001).
Medline CASGoogle Scholar
4 Bisht S, Bhakta G, Mitra S, Maitra A. pDNA loaded calcium phosphate nanoparticles: highly efficient non-viral vector for gene delivery. Int. J. Pharm.288(1),157–168 (2005).
Medline CASGoogle Scholar
5 Khosravi-Darani K, Mozafari MR, Rashidi L, Mohammadi M. Calcium based non-viral gene delivery: an overview of methodology and applications. Acta Med. Iran.48(3),133–141 (2010).
Medline CASGoogle Scholar
6 Kumta PN, Sfeir C, Lee D-H, Olton D, Choi D. Nanostructured calcium phosphates for biomedical applications: novel synthesis and characterization. Acta Biomater.1(1),65–83 (2005).
MedlineGoogle Scholar
7 Douglas KL. Toward development of artificial viruses for gene therapy: a comparative evaluation of viral and non-viral transfection. Biotechnol. Prog.24(4),871–883 (2008).
Medline CASGoogle Scholar
8 Ditto AJ, Shah PN, Gump LR, Yun YH. Nanospheres formulated from L-tyrosine polyphosphate exhibiting sustained release of polyplexes and in vitro controlled transfection properties. Mol. Pharm.6(3),986–995 (2009).
Medline CASGoogle Scholar
9 Liu T, Tang A, Zhang G et al. Calcium phosphate nanoparticles as a novel nonviral vector for efficient transfection of DNA in cancer gene therapy. Cancer Biother. Radiopharm.20(2),141–149 (2005).
Medline CASGoogle Scholar
10 Yang J-P, Huang L. Overcoming the inhibitory effect of serum on lipofection by increasing the charge ratio of cationic liposome to DNA. Gene Ther.4,950–960 (1997).
Medline CASGoogle Scholar
11 Morille M, Passirani C, Vonarbourg A, Clavreul A, Benoit JP. Progress in developing cationic vectors for non-viral systemic gene therapy against cancer. Biomaterials29(24–25),3477–3496 (2008).
Medline CASGoogle Scholar
12 Liu F, Huang L. Development of non-viral vectors for systemic gene delivery. J. Control. Release78(1–3),259–266 (2002).
Medline CASGoogle Scholar
13 Dang JM, Leong KW. Natural polymers for gene delivery and tissue engineering. Adv. Drug Deliv. Rev.58(4),487–499 (2006).
Medline CASGoogle Scholar
14 Lee KY. Chitosan and its derivatives for gene delivery. Macromol. Res.15(3),195–201 (2007).
CASGoogle Scholar
15 Kim TH, Jiang HL, Jere D et al. Chemical modification of chitosan as a gene carrier in vitro and in vivo. Prog. Polym. Sci.32(7),726–753 (2007).
CASGoogle Scholar
16 Lacerda L, Raffa S, Prato M, Bianco A, Kostarelos K. Cell-penetrating CNTs for delivery of therapeutics. Nano Today2(6),38–43 (2007).
Google Scholar
17 Maitra A. Calcium phosphate nanoparticles: second-generation nonviral vectors in gene therapy. Exp. Rev. Mol. Diagnos.5(6),893–905 (2005).
Medline CASGoogle Scholar
18 Zhu SH, Huang BY, Zhou KC et al. Hydroxyapatite nanoparticles as a novel gene carrier. J. Nanopart. Res.6(2–3),307–311 (2004).
CASGoogle Scholar
19 Haberland A, Knaus T, Zaitsev SV et al. Calcium ions as efficient cofactor of polycation-mediated gene transfer. Biochim. Biophys. Acta Gene Struct. Express.1445(1),21–30 (1999).
Medline CASGoogle Scholar
20 Truong-Le VL, Walsh SM, Schweibert E et al. Gene transfer by DNA-gelatin nanospheres. Arch. Biochem. Biophys.361(1),47–56 (1999).
Medline CASGoogle Scholar
21 Lee MA, Dunn RC, Clapham DE, Stehno-Bittel L. Calcium regulation of nuclear pore permeability. Cell Calcium23(2–3),91–101 (1998).
Medline CASGoogle Scholar
22 Puvvada N, Panigrahi PK, Pathak A. Room temperature synthesis of highly hemocompatible hydroxyapatite, study of their physical properties and spectroscopic correlation of particle size. Nanoscale2(12),2631–2638 (2010).
Medline CASGoogle Scholar
23 Rohanizadeh R, Trecant-Viana M, Daculsi G. Ultrastructural study of apatite precipitation in implanted calcium phosphate ceramic: influence of the implantation site. Calcif. Tissue Int.64(5),430–436 (1999).▪ Demonstrated how the dissolution/reprecipitation process in bioceramic implants is modulated by two selected implantation sites.
Medline CASGoogle Scholar
24 Rohanizadeh R, Chung K. Hydroxyapatite as a carrier for bone morphogenetic protein. J. Oral Implantol.37(6),659–672 (2011).▪▪ Compared different methods to load bone morphogenetic protein (BMP) into hydroxyapatite (HA) carriers, and showed that BMP incorporation during HA precipitation resulted in a sustained and prolonged BMP release.
MedlineGoogle Scholar
25 Rohanizadeh R, Padrines M, Bouler JM, Couchourel D, Fortun Y, Daculsi G. Apatite precipitation after incubation of biphasic calcium-phosphate ceramic in various solutions: influence of seed species and proteins. J. Biomed. Mater. Res.42(4),530–539 (1998).▪▪ Showed the influences of selected proteins and two ceramic phases (HA and tri-calcium phosphate) on the stability of biphasic bioceramic implants.
Medline CASGoogle Scholar
26 Kumar R, Prakash KH, Cheang P, Khor KA. Temperature driven morphological changes of chemically precipitated hydroxyapatite nanoparticles. Langmuir20(13),5196–5200 (2004).
Medline CASGoogle Scholar
27 Han Y, Wang X, Li S. A simple route to prepare stable hydroxyapatite nanoparticles suspension. J. Nanopart. Rese.11(5),1235–1240 (2009).
CASGoogle Scholar
28 Zhu SH, Huang BY, Zhou KC et al. Hydroxyapatite nanoparticles as a novel gene carrier. J. Nanopart. Res.6(2),307–311 (2004).
CASGoogle Scholar
29 Uskokovic V, Uskokovic DP. Nanosized hydroxyapatite and other calcium phosphates: chemistry of formation and application as drug and gene delivery agents. J. Biomed. Mater. Res. Part B Appl. Biomater.96(1),152–191 (2011).
MedlineGoogle Scholar
30 Motskin M, Wright DM, Muller K et al. Hydroxyapatite nano and microparticles. Correlation of particle properties with cytotoxicity and biostability. Biomaterials30(19),3307–3317 (2009).
Medline CASGoogle Scholar
31 Cai Y, Liu Y, Yan W et al. Role of hydroxyapatite nanoparticle size in bone cell proliferation. J. Mater. Chem.17(36),3780–3787 (2007).
CASGoogle Scholar
32 Brigger I, Dubernet C, Couvreur P. Nanoparticles in cancer therapy and diagnosis. Adv. Drug Deliv. Rev.54(5),631–651 (2002).
Medline CASGoogle Scholar
33 Tousignant JD, Gates AL, Ingram LA et al. Comprehensive analysis of the acute toxicities induced by systemic administration of cationic lipid. Plasmid DNA complexes in mice. Hum. Gene Ther.11(18),2493–2513 (2000).
Medline CASGoogle Scholar
34 Chen L, Mccrate JM, Lee JC-M, Li H. The role of surface charge on the uptake and biocompatibility of hydroxyapatite nanoparticles with osteoblast cells. Nanotechnol.22(10),105708 (2011).
MedlineGoogle Scholar
35 Gratton SEA, Ropp PA, Pohlhaus PD et al. The effect of particle design on cellular internalization pathways. Proc. Natl Acad. Sci. USA105(33),11613–11618 (2008).
Medline CASGoogle Scholar
36 Daculsi G, Bouler JM, Legeros RZ. Adaptive crystal formation in normal and pathological calcifications in synthetic calcium phosphate and related biomaterials. Int. Rev. Cytol.172,129–191 (1997).
Medline CASGoogle Scholar
37 Zhao Y, Zhang Y, Ning F, Guo D, Xu Z. Synthesis and cellular biocompatibility of two kinds of HAP with different nanocrystal morphology. J. Biomed. Mater. Res. Part B Appl. Biomater.83(1),121–126 (2007).
MedlineGoogle Scholar
38 Zhang Y, Lu J. A simple method to tailor spherical nanocrystal hydroxyapatite at low temperature. J. Nanopart. Res.9(4),589–594 (2007).
CASGoogle Scholar
39 Padilla S, Izquierdo-Barba I, Vallet-Regí M. High specific surface area in nanometric carbonated hydroxyapatite. Chem. Mater.20(19),5942–5944 (2008).
CASGoogle Scholar
40 Pramanik N, Tarafdar A, Pramanik P. Capping agent-assisted synthesis of nanosized hydroxyapatite: comparative studies of their physicochemical properties. J. Mater. Process. Technol.184(1–3),131–138 (2007).
CASGoogle Scholar
41 Shi Z, Huang X, Cai Y, Tang R, Yang D. Size effect of hydroxyapatite nanoparticles on proliferation and apoptosis of osteoblast-like cells. Acta Biomater.5(1),338–345 (2009).
Medline CASGoogle Scholar
42 Bose S, Saha SK. Synthesis and Characterization of hydroxyapatite nanopowders by emulsion technique. Chem. Mater.15(23),4464–4469 (2003).
CASGoogle Scholar
43 Li H, Zhu M, Li L, Zhou C. Processing of nanocrystalline hydroxyapatite particles via reverse microemulsions. J. Mater. Sci.43(1),384–389 (2008).
CASGoogle Scholar
44 Sun Y, Guo G, Tao D, Wang Z. Reverse microemulsion-directed synthesis of hydroxyapatite nanoparticles under hydrothermal conditions. J. Physics Chem. Solids68(3),373–377 (2007).
CASGoogle Scholar
45 Dasgupta S, Bandyopadhyay A, Bose S. Reverse micelle-mediated synthesis of calcium phosphate nanocarriers for controlled release of bovine serum albumin. Acta Biomater.5(8),3112–3121 (2009).
Medline CASGoogle Scholar
46 Gonzalez-Mcquire R, Chane-Ching J-Y, Vignaud E, Lebugle A, Mann S. Synthesis and characterization of amino acid-functionalized hydroxyapatite nanorods. J. Mater. Chem.14(14),2277–2281 (2004).
CASGoogle Scholar
47 Rohanizadeh R, Legeros RZ, Harsono M, Bendavid A. Adherent apatite coating on titanium substrate using chemical deposition. J. Biomed. Mater. Res. A72(4),428–438 (2005).
Medline CASGoogle Scholar
48 Zavgorodniy AV, Borrero-Lopez O, Hoffman M, Legeros RZ, Rohanizadeh R. Mechanical stability of two-step chemically deposited hydroxyapatite coating on Ti substrate: effects of various surface pretreatments. J. Biomed. Mater. Res. B Appl. Biomater.99(1),58–69 (2011).▪▪ Demonstrated a novel chemical deposition method by hydrothermal conversion of monetite to HA, which produced an adherent ceramic coating on Ti implants.
MedlineGoogle Scholar
49 Zavgorodniy AV, Borrero-Lopez O, Hoffman M, Legeros RZ, Rohanizadeh R. Characterization of the chemically deposited hydroxyapatite coating on a titanium substrate. J. Mater. Sci. Mater. Med.22(1),1–9 (2011).
Medline CASGoogle Scholar
50 Chu CL, Lin PH, Dong YS, Guo DY. Influences of citric acid as a chelating reagent on the characteristics of nanophase hydroxyapatite powders fabricated by a sol-gel method. J. Mater. Sci. Lett.21(22),1793–1795 (2002).
CASGoogle Scholar
51 Liu J, Li K, Wang H, Zhu M, Xu H, Yan H. Self-assembly of hydroxyapatite nanostructures by microwave irradiation. Nanotechnology16(1),82–87 (2005).
CASGoogle Scholar
52 Uota M, Arakawa H, Kitamura N, Yoshimura T, Tanaka J, Kijima T. Synthesis of high surface area hydroxyapatite nanoparticles by mixed surfactant-mediated approach. Langmuir21(10),4724–4728 (2005).
Medline CASGoogle Scholar
53 Morgan TT, Muddana HS, Altinoglu EI et al. Encapsulation of organic molecules in calcium phosphate nanocomposite particles for intracellular imaging and drug delivery. Nano Lett.8(12),4108–4115 (2008).
Medline CASGoogle Scholar
54 Zhang MM, Zhai H, Liu H, Liu J, Han X, He W. A novel mixed hydroxide method for hydroxyapatite preparation. Adv. Mater. Res.152–153, 1399–1403 (2011).
CASGoogle Scholar
55 Chow LC, Sun L, Hockey B. Properties of nanostructured hydroxyapatite prepared by a spray drying technique. J. Res. Natl Inst. Stand. Technol.109(6),543–551 (2004).
Medline CASGoogle Scholar
56 Kandori K, Kuroda T, Togashi S, Katayama E. Preparation of calcium hydroxyapatite nanoparticles using microreactor and their characteristics of protein adsorption. J. Phys. Chem. B115(4),653–659 (2011).
Medline CASGoogle Scholar
57 Han YC, Wang XY, Li SP. A simple route to prepare stable hydroxyapatite nanoparticles suspension. J. Nanopart. Res.11(5),1235–1240 (2009).
CASGoogle Scholar
58 Alatorre-Meda M, Taboada P, Sabin J, Krajewska B, Varela LM, Rodriguez JR. DNA-chitosan complexation: a dynamic light scattering study. Coll. Surf. A Physicochem. Eng. Aspects339(1–3),145–152 (2009).
CASGoogle Scholar
59 Sokolova VV, Radtke I, Heumann R, Epple M. Effective transfection of cells with multi-shell calcium phosphate-DNA nanoparticles. Biomaterials27(16),3147–3153 (2006).
Medline CASGoogle Scholar
60 Wang F, Li MS, Lu YP, Qi YX. A simple sol-gel technique for preparing hydroxyapatite nanopowders. Mater. Lett.59(8–9),916–919 (2005).
CASGoogle Scholar
61 Gopi D, Govindaraju KM, Victor Ca, Kavitha L, Rajendiran N. Spectroscopic investigations of nanohydroxyapatite powders synthesized by conventional and ultrasonic coupled sol-gel routes. Spectrochim. Acta Part A Mol. Biomol. Spectrosc.70(5),1243–1245 (2008).
Medline CASGoogle Scholar
62 Kim IS, Kumta PN. Sol-gel synthesis and characterization of nanostructured hydroxyapatite powder. Mater. Sci. Eng. B Solid State Mater. Adv. Technol.111(2–3),232–236 (2004).
Google Scholar
63 Muddana HS, Morgan TT, Adair JH, Butler PJ. Photophysics of Cy3-encapsulated calcium phosphate nanoparticles. Nano Lett.9(4),1559–1566 (2009).
Medline CASGoogle Scholar
64 Kester M, Heakal Y, Fox T et al. Calcium phosphate nanocomposite particles for in vitro imaging and encapsulated chemotherapeutic drug delivery to cancer cells. Nano Lett.8(12),4116–4121 (2008).
Medline CASGoogle Scholar
65 Wang A, Liu D, Yin H et al. Size-controlled synthesis of hydroxyapatite nanorods by chemical precipitation in the presence of organic modifiers. Mater. Sci. Eng. C27(4),865–869 (2007).
CASGoogle Scholar
66 Yan L, Li Y, Deng Z-X, Zhuang J, Sun X. Surfactant-assisted hydrothermal synthesis of hydroxyapatite nanorods. Int. J. Inorg. Mater.3(7),633–637 (2001).
CASGoogle Scholar
67 Earl JS, Wood DJ, Milne SJ. Hydrothermal synthesis of hydroxyapatite. J. Phys. Confer. Ser.26(1),268–271 (2006).
Google Scholar
68 Yang Q, Wang J-X, Shao L et al. High throughput methodology for continuous preparation of hydroxyapatite nanoparticles in a microporous tube-in-tube microchannel reactor. Ind. Eng. Chem. Res.49(1),140–147 (2009).
CASGoogle Scholar
69 Lee WH, Zavgorodniy AV, Loo CY, Rohanizadeh R. Synthesis and characterization of hydroxyapatite with different crystallinity: effects on protein adsorption and release. J. Biomed. Mater. Res. Part A doi:10.1002/jbm.a.34093 (2012) (Epub ahead of print).▪▪ Demonstrated that proteins had a greater tendency to bind onto amorphous calcium phosphate than crystalline HA and the adsorption rate was negatively correlated to the crystallinity rate of HA.
Google Scholar
70 Bhattarai SR, Kim SY, Jang KY et al. Laboratory formulated magnetic nanoparticles for enhancement of viral gene expression in suspension cell line. J. Virol. Methods147(2),213–218 (2008).
Medline CASGoogle Scholar
71 Lee CM, Park JW, Kim J, Kim DW, Jeong HJ, Lee KY. Influence of histidine on the release of all-trans retinoic acid from self-assembled glycol chitosan nanoparticles. Drug Dev. Ind. Pharm.36(7),781–786 (2010).
Medline CASGoogle Scholar
72 Wang P, Li C, Gong H, Jiang X, Wang H, Li K. Effects of synthesis conditions on the morphology of hydroxyapatite nanoparticles produced by wet chemical process. Powder Technol.203(2),315–321 (2010).
CASGoogle Scholar
73 Lee WH, Loo CY, Van KL, Zavgorodniy AV, Rohanizadeh R. Modulating protein adsorption onto hydroxyapatite particles using different amino acid treatments. J. R. Soc. Interface9(70),918–927 (2011).▪▪ Showed that the immobilization of different amino acids onto a HA drug carrier can tailor the surface charge of the HA and provide selective binding sites for specific therapeutic proteins.
MedlineGoogle Scholar

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Published online 17 May 2012

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Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

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Hydroxyapatite nanoparticles as vectors for gene delivery

Abstract

References