新型基因治疗载体——纳米羟基磷灰石
New Gene Therapy Vector—Nano-Hydroxyapatite
摘要: 羟基磷灰石(Hydroxyapatite, Hap)是脊椎动物骨、牙中的天然组分，它具有优异的生物相容性和良好的生物降解性，是目前可通过化学调控大量合成无机生物材料，已被广泛用于硬组织修复材料、药物缓释载体材料等。本文详细综述了近年来纳米羟基磷灰石在基因治疗载体领域的研究进展，阐述了其用于基因治疗载体的转染机制、生物安全性、化学合成的可控性、可降解性及其靶向性等。
Abstract: Hydroxyapatite (HAp) is the natural inorganic component of vertebrate bone and tooth tissues. It is currently one of the most important inorganic biological materials what can be synthesized by chemical regulation in large amounts. In recent years, owing to its good biocompatibility, excellent biodegradability and chemical synthesis of controllability, it received more and more attention in the application of hard tissue repair materials and drug controlled release vectors. This article reviews its transfection mechanism, biosecurity, controllability of chemical synthesis, biodegradability and targeting used as gene therapy vectors.
文章引用：须苏菊, 孔祥东, 赵瑞波, 韩华锋. 新型基因治疗载体——纳米羟基磷灰石[J]. 材料科学, 2013, 3(1): 11-15. http://dx.doi.org/10.12677/MS.2013.31003

参考文献

[1] A. P. Cotrim, B. J. Baum. Gene therapy: Some history, appli- cations, problems, and prospects. Toxicologic Pathology, 2008, 36(1): 97-103.
[2] Y. Hattori. Development of non-viral vector for cancer gene therapy. Yakugaku Zasshi, 2010, 130(7): 917-923.
[3] J. W. B. Bainbridge, A. J. Smith, S. S. Barker, S. Robbie, R. Henderson, K. Balaggan, et al. Effect of gene therapy on visual function in Leber’s congenital amaurosis. The New England Journal of Medicine, 2008, 358(21): 2231-2239.
[4] M. L. Edelstein, M. R. Abedi and J. Wixon. Gene therapy clini- cal trials worldwide to 2007—An update. The Journal of Gene Medicine, 2007, 9(10): 833-842.
[5] S. Daya, K. I. Berns. Gene therapy using adeno-associated virus vectors. Clinical Microbiology Reviews, 2008, 21(4): 583-593.
[6] H. Herweijer, J. A. Wolff. Gene therapy progress and prospects: hydrodynamic gene delivery. Gene Therapy, 2007, 14(2): 99- 107.
[7] A. Mohyeldin, E. A. Chiocca. Gene and viral therapy for gliob- lastoma: A review of clinical trials and future directions. Cancer Journal, 2012, 18(1): 82-88.
[8] C. Strambio-De-Castillia, M. Niepel and M. P. Rout. The nuclear pore complex: Bridging nuclear transport and gene regulation. Nature Reviews. Molecular Cell Biology, 2010, 11(7): 490-501.
[9] L. E. Vinge, P. W. Raake and W. J. Koch. Gene therapy in heart failure. Circulation Research, 2008, 102(12): 1458-1470.
[10] M. S. Al-Dosari, X. Gao. Nonviral gene delivery: Principle, limitations, and recent progress. AAPS Journal, 2009, 11(4): 671- 681.
[11] M. Donkuru, I. Badea, S. Wettig, R. Verrall, M. Elsabahy and M. Foldvari. Advancing nonviral gene delivery: Lipid- and surface-tant-based nanoparticle design strategies. Nanomedicine, 2010, 5(7): 1103-1127.
[12] K. Gao, L. Huang. Nonviral methods for siRNA delivery. Mo- lecular Pharmaceutics, 2009, 6(3): 651-658.
[13] X. Kong, S. Xu, X. Wang, F. Cui and J. Yao. Calcium carbonate microparticles used as a gene vector for delivering p53 gene into cancer cells. Journal of Biomedical Materials Research. Part A, 2012, 100(9): 2312-2318.
[14] I. Roy, M. K. Stachowiak and E. J. Bergey. Nonviral gene trans- fection nanoparticles: Function and applications in the brain. Nanomedicine: Nanotechnology, Biology, and Medicine, 2008, 4(2): 89-97.
[15] N. G. Abraham, A. Asija, G. Drummond and S. Peterson. Heme oxygenase-1 gene therapy: Recent advances and therapeutic ap- plications. Current Gene Therapy, 2007, 7(2): 89-108.
[16] S. M. Conley, X. Cai and M. I. Naash. Nonviral ocular gene the- rapy: Assessment and future directions. Current Opinion in Mo- lecular Therapeutics, 2008, 10(5): 456-463.
[17] H. Urch, M. Vallet-Regi, L. Ruiz, J. M. Gonzalez-Calbet and M. Epple. Calcium phosphate nanoparticles with adjustable disper- sability and crystallinity. Journal of Materials Chemistry, 2009, 19(15): 2166-2171.
[18] V. Uskokovic, D. P. Uskokovic. Nanosized hydroxyapatite and other calcium phosphates: Chemistry of formation and applica- tion as drug and gene delivery agents. Journal of Biomedical Materials Research. Part B, 2011, 96(1): 152-191.
[19] R. Z. LeGeros. Calcium phosphate-based osteoinductive materi- als. Chemical Reviews, 2008, 108(11): 4742-4753.
[20] G. M. Cunniffe, F. J. O’Brien, S. Partap, T. J. Levingstone, K. T. Stanton and G. R. Dickson. The synthesis and characterization of nanophase hydroxyapatite using a novel dispersant-aided pre- cipitation method. Journal of Biomedical Materials Research. Part A, 2010, 95(4): 1142-1149.
[21] E. T. Castellana, P. S. Cremer. Solid supported lipid bilayers: From biophysical studies to sensor design. Surface Science, 2006, 61(10): 429-444.
[22] 李新新, 侯森, 冯喜增. 无机纳米粒子作为基因载体的研究进展. 生命科学, 2008, 20(3): 402-407.
[23] V. Sokolova, M. Epple. Inorganic nanoparticles as carriers of nucleic acids into cells. Angewandte Chemie, International Edi- tion, 2008, 47(8): 1382-1395.
[24] A. Kovtun, R. Heumann and M. Epple. Calcium phosphate na- noparticles for the transfection of cells. Bio-Medical Materials and Engineering, 2009, 19(2-3): 241-247.
[25] M. Brisson, W. C. Tseng, C. Almonte, S. Watkins and L. Huang. Subcellular trafficking of the cytoplasmic expression system. Human Gene Therapy, 1999, 10(16): 2601-2613.
[26] A. H. Faraji, P. Wipf. Nanoparticles in cellular drug delivery. Bioorganic & Medicinal Chemisty, 2009, 17(8): 2950-2962.
[27] R. B. Huang, S. Mocherla, M. J. Heslinga, P. Charoenphol and O. Eniola-Adefeso. Dynamic and cellular interactions of nanoparti- cles in vascular-targeted drug delivery (review). Molecular Membrane Biology, 2010, 27(7): 312-327.
[28] S. Bisht, G. Bhakta, S. Mitra and A. Maitra. pDNA loaded cal- cium phosphate nanoparticles: Highly efficient non-viral vector for gene delivery. International Journal of Pharmaceutics, 2005, 288(1): 157-168.
[29] S. Elangovan, S. Jain, P. C. Tsai, H. C. Margolis and M. Amiji. Nano-sized calcium phosphate particles for periodontal gene the- rapy. Journal of Periodontology, 2012, 84(1): 117-125.
[30] B. D. Hahn, J. M. Lee, D. S. Park, J. J. Choi, J. Ryu W. H. Yoon, et al. Enhanced bioactivity and biocompatibility of nanostruc- tured hydroxyapatite coating by hydrothermal annealing. Thin Solid Films, 2011, 519(22): 8085-8090.
[31] G. Li, L. Ye, J. Pan, M. Long, Z. Zhao, H. Yang, et al. Antitu- moural hydroxyapatite nanoparticles-mediated hepatoma-tar- geted trans-arterial embolization gene therapy: In vitro and in vivo studies. Liver International, 2012, 32(6): 998-1007.
[32] B. Muller. Tailoring biocompatibility: Benefitting patients. Ma- terials Today, 2010, 13(4): 58.
[33] M. Motskin, D. M. Wright, K. Muller, N. Kyle, T. G. Gard, A. E. Porter, et al. Hydroxyapatite nano and microparticles: Correla- tion of particle properties with cytotoxicity and biostability. Biomaterials, 2009, 30(19): 3307-3317.
[34] L. A. Chen, J. M. Mccrate, J. C. M. Lee and H. Li. The role of surface charge on the uptake and biocompatibility of hydroxya- patite nanoparticles with osteoblast cells. Nanotechnology, 2011, 22(10): Article ID: 105708.
[35] M. Kester, Y. Heakal, T. Fox, A. Sharma, G. P. Robertson, T. T. Morgan, et al. Calcium phosphate nanocomposite particles for in vitro imaging and encapsulated chemotherapeutic drug delivery to cancer cells. Nano Letters, 2008, 8(12): 4116-4121.
[36] Q. Zhang, D. Zhao, X. Z. Zhang, S. X. Cheng and R. X. Zhuo. Calcium phosphate/DNA co-precipitates encapsulated fast-deg- rading polymer films for substrate-mediated gene delivery. Jour- nal of Biomedical Materials Research. Part B, 2009, 91(1): 172-180.
[37] J. Li, Y. C. Chen, Y. C. Tseng, S. Mozumdar and L. Huang. Biodegradable calcium phosphate nanoparticle with lipid coat- ing for systemic siRNA delivery. Journal of Controlled Release, 2010, 142(3): 416-421.
[38] E. H. Chowdhury, A. Maruyama, A. Kano, M. Nagaoka, M. Ko- taka, S. Hirose, et al. pH-sensing nano-crystals of carbonate apa- tite: Effects on intracellular delivery and release of DNA for ef- ficient expression into mammalian cells. Gene, 2006, 376(1): 87-94.
[39] Z. P. Xu, Q. H. Zeng, G. Q. Lu and A. B. Yu. Inorganic nanopar- ticles as carriers for efficient cellular delivery. Chemical Engi- neering Science, 2006, 61(3): 1027-1040.
[40] I. Nadra, A. R. Boccaccini, P. Philippidis, L. C. Whelan, G. M. McCarthy, D. O. Haskard, et al. Effect of particle size on hy- droxyapatite crystal-induced tumor necrosis factor alpha secre- tion by macrophages. Atherosclerosis, 2008, 196(1): 98-105.
[41] S. E. A. Gratton, P. A. Ropp, P. D. Pohlhaus, J. C. Luft, V. J. Ma- dden, M. E. Napier, et al. The effect of particle design on cellu- lar internalization pathways. Proceedings of the National Aca- demy of Sciences of the USA, 2008, 105(33): 11613-11618.
[42] B. D. Chithrani, W. C. W. Chan. Elucidating the mechanism of cellular uptake and removal of protein-coated gold nanoparticles of different sizes and shapes. Nano Letters, 2007, 7(6): 1542- 1550.
[43] X. L. Huang, X. Teng, D. Chen, F. Q. Tang and J. Q. He. The effect of the shape of mesoporous silica nanoparticles on cellular uptake and cell function. Biomaterials, 2010, 31(3): 438-448.
[44] J. M. Oh, S. J. Choi, G. E. Lee, S. H. Han and J. H. Choy. Inor- ganic drug-delivery nanovehicle conjugated with cancer-cell- specific ligand. Advanced Functional Materials, 2009, 19(10): 1617-1624.
[45] G. Zuber, L. Zammut-Italiano, E. Dauty and J. P. Behr. Targeted gene delivery to cancer cells: Directed assembly of nanometric DNA particles coated with folic acid. Angewandte Chemie In- ternational Edition, 2003, 42(23): 2666-2669.
[46] T. N. Do, W. H. Lee, C. Y. Loo, A. V. Zavgorodniy and R. Roha- nizadeh. Hydroxyapatite nanoparticles as vectors for gene deliv- ery. Therapeutic Delivery, 2012, 3(5): 623-632.
[47] D. Olton, J. H. Li, M. E. Wilson, T. Rogers, J. Close, L. Huang, et al. Nanostructured calcium phosphates (NanoCaPs) for non- viral gene delivery: Influence of the synthesis parameters on transfection efficiency. Biomaterials, 2007, 28(6): 1267-1279.
[48] G. Zuo, Y. Wan and Y. Zhang. Preparation and characterization of a novel laminated magnetic hydroxyapatite for application on gene delivery. Materials Letters, 2012, 68: 225-227.
[49] B. Sumer, J. M. Gao. Theranostic nanomedicine for cancer. Na- nomedicine, 2008, 3(2): 137-140.
[50] F. Ye, H. Guo and H. Zhang. Biomimetic synthesis of oriented hydroxyapatite mediated by nonionic surfactants. Nanotechnol- ogy, 2008, 19(24): Article ID: 245605.

为你推荐