Nanostructured calcium phosphates for biomedical applications: novel synthesis and characterization
Nanostructured calcium phosphates for biomedical applications: novel synthesis and characterization
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DOI：
10.1016/j.actbio.2004.09.008
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发表时间：
2005-01-01
影响因子：
9.7
通讯作者：
Choi, D
中科院分区：
文献类型：
--
作者：
Kumta, PN;Sfeir, C;Choi, D
材料在几种生物医学应用中起着关键作用，为了获得成功的生物学结果，必须清楚地了解材料和生物学方面。本文阐述了我们实现磷酸钙作为基因递送剂的方法。磷酸钙(CaP)属于生物相容性磷灰石家族，有几种CaP相，其中最普遍的是羟基磷灰石(HAP，Ca-10(PO4)(6)(OH)(2))。其他帽子结构包括刷石(B，CaHPO4(.)2H(2)O)和磷酸三钙(Tcp，Ca-3(PO4)(2))。已有报道了几种合成羟基磷灰石和水滑石的低温和高温方法，而磷酸三钙主要是用高温方法合成的。我们开发了一种新的低温化学方法来合成纳米结构的HAP、水滑石和TCP相。新的低温方法导致在生理条件下形成化学计量比的纳米羟基磷灰石。此外，合成方法被设计为与细胞、DNA和蛋白质等生物系统生物相容，从而可以研究帽子结构以用于基因传递。HAP类型的CAP相用于基因传递是众所周知的，但据我们所知，由于缺乏生物相容的合成方法，其他形式的CAP还没有被研究用于基因传递。除了帽子结构的生物相容性合成，我们还进行了离子取代，这将为我们提供适当的工具来研究DNA与粒子的相互作用，并评估这些离子取代将如何影响细胞对DNA的摄取水平，然后将其释放到细胞核。14%的镁替代钙会形成结晶(类似于20微米)的刷石小片，在pH 7.5下保持稳定。进一步的取代得到了独特的纳米结构的球状刷石，从中可以生长出高比表面积(类似于200m(2)/g)的纳米晶(类似于80 nm)的β-TCMP相。其新奇之处在于在生理条件下形成稳定的HAP、刷石和β-TCMP相，使它们有可能作为非病毒基因传递的载体或更广泛的生物系统使用。对合成的纳米磷酸盐的结构、形貌、热稳定性和组成进行了表征。还描述了体外转染法的结果。(C)2004年Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Materials play a key role in several biomedical applications, and it is imperative that both the materials and biological aspects are clearly understood for attaining a successful biological outcome. This paper illustrates our approach to implement calcium phosphates as gene delivery agents. Calcium phosphates (CaP) belong to the family of biocompatible apatites and there are several CaP phases, the most ubiquitous being hydroxyapatite (HAp, Ca-10(PO4)(6)(OH)(2). Other CaP structures include brushite (B, CaHPO4 (.) 2H(2)O) and tricalcium phosphate (TCP, Ca-3(PO4)(2)). Several low and high temperature approaches have been reported for synthesizing HAp and brushite, while TCP is primarily synthesized using high temperature methods. Novel low temperature chemical methods have been developed by us to synthesize nanostructured HAp, brushite and TCP phases. The new low temperature approach results in the formation of stoichiometric and nanosized HAp under physiological conditions. Moreover, the synthesis methods were designed to be biocompatible with biological systems such as cells, DNA and proteins so that the CaP structures can be studied for gene delivery. The use of HAp type CaP phases for gene delivery is well known but to our knowledge, other forms of CaP have not been studied for gene delivery due to the lack of a biocompatible synthesis method. In addition to the biocompatible synthesis of CaP structures, we have also performed ion substitution that would provide us the appropriate tools to study the DNA-to-particle interactions and assess how these ionic substitutions would affect the level of DNA uptake by the cell and then its release to the cell nucleus.Substitution of calcium by 14% magnesium results in the formation of crystalline (similar to 20 mu m) brushite platelets that remains stable at pH 7.5. Further substitution results in unique nanostructured spherical morphologies of brushite from which rosette shaped high specific surface area (similar to 200m(2)/g) nanocrystals (similar to 80 nm) of beta-TCMP phase can be grown. The novelty lies in the formation of stable phases of HAp, brushite and beta-TCMP under physiological conditions making them potential candidates for use as carriers for non-viral gene delivery or more generally in biological systems. The resultant nanocrystalline phosphates have been characterized for their structure, morphology, thermal stability, and composition. Results of the in vitro transfection are also described. (c) 2004 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.