{"title":"Direct Immobilization of Folic Acid Molecules on Hydroxyapatite Nanoparticles with Substitution and Coordination Phenomena.","authors":"Wanyu Shi, Shoma Hatori, Daichi Noda, Iori Yamada, Motohiro Tagaya","doi":"10.1021/acsbiomaterials.4c01146","DOIUrl":null,"url":null,"abstract":"<p><p>We successfully synthesized folic acid (FA) immobilized hydroxyapatite (HA) nanoparticles without using a mediative reagent (e.g., silane coupling agent), and the immobilization states were evaluated and discussed. The HA nanoparticles with higher biocompatibility have two different planes, namely, <i>c</i>- and <i>m</i>-planes. These plane surfaces are rich in phosphate groups (P-site) and Ca<sup>2+</sup> ions (C-site), respectively. We suggested that during the synthesis of the HA nanoparticles, the P-site substitution and C-site coordination with the addition of organic molecules containing -COO<sup>-</sup> ions can occur. Thus, it is possible to simultaneously immobilize two molecules to one HA nanoparticle. In this study, we successfully synthesized FA-immobilized HA nanoparticles by P-site substitution and C-site coordination reactions, which were named as substitution type and coordination type. In the substitution type, when FA was reacted with HA during the nucleation stage, the PO<sub>4</sub><sup>3-</sup> ions of HA decreased as the FA ratio of coverage surface area increased, and the crystalline phase was changed significantly from the Ca deficient HA to the carbonated HA phase. Accordingly, it was indicated that FA was immobilized on HA by the P-site substitution. In the coordination type, since FA was reacted with HA after the completion of crystal growth, the crystalline phase was changed slightly as the FA ratio of coverage surface area increased, indicating that FA was immobilized on HA by the C-site coordination. From the above, we controlled the FA immobilization states on the HA nanoparticles by the P-site substitution and the C-site coordination through the FA addition timing in the synthesis. Since the -COO<sup>-</sup> ions in FA could be selectively substituted with the P-site in HA, it is possible to directly coordinate the foreign organic molecules to the Ca<sup>2+</sup> ions in HA. Therefore, the immobilization technique of this study is expected to achieve two different drug molecules with diagnosis and therapy functions (i.e., theranostics) on one nanoparticle.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4000,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Biomaterials Science & Engineering","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1021/acsbiomaterials.4c01146","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
引用次数: 0
Abstract
We successfully synthesized folic acid (FA) immobilized hydroxyapatite (HA) nanoparticles without using a mediative reagent (e.g., silane coupling agent), and the immobilization states were evaluated and discussed. The HA nanoparticles with higher biocompatibility have two different planes, namely, c- and m-planes. These plane surfaces are rich in phosphate groups (P-site) and Ca2+ ions (C-site), respectively. We suggested that during the synthesis of the HA nanoparticles, the P-site substitution and C-site coordination with the addition of organic molecules containing -COO- ions can occur. Thus, it is possible to simultaneously immobilize two molecules to one HA nanoparticle. In this study, we successfully synthesized FA-immobilized HA nanoparticles by P-site substitution and C-site coordination reactions, which were named as substitution type and coordination type. In the substitution type, when FA was reacted with HA during the nucleation stage, the PO43- ions of HA decreased as the FA ratio of coverage surface area increased, and the crystalline phase was changed significantly from the Ca deficient HA to the carbonated HA phase. Accordingly, it was indicated that FA was immobilized on HA by the P-site substitution. In the coordination type, since FA was reacted with HA after the completion of crystal growth, the crystalline phase was changed slightly as the FA ratio of coverage surface area increased, indicating that FA was immobilized on HA by the C-site coordination. From the above, we controlled the FA immobilization states on the HA nanoparticles by the P-site substitution and the C-site coordination through the FA addition timing in the synthesis. Since the -COO- ions in FA could be selectively substituted with the P-site in HA, it is possible to directly coordinate the foreign organic molecules to the Ca2+ ions in HA. Therefore, the immobilization technique of this study is expected to achieve two different drug molecules with diagnosis and therapy functions (i.e., theranostics) on one nanoparticle.
我们成功合成了叶酸(FA)固定化羟基磷灰石(HA)纳米粒子,无需使用介导试剂(如硅烷偶联剂),并对其固定化状态进行了评估和讨论。生物相容性较高的 HA 纳米粒子具有两个不同的平面,即 c 平面和 m 平面。这些平面表面分别富含磷酸基团(P 位)和 Ca2+ 离子(C 位)。我们认为,在合成 HA 纳米粒子的过程中,可以通过添加含有 -COO- 离子的有机分子来实现 P 位取代和 C 位配位。因此,在一个 HA 纳米粒子上同时固定两个分子是可能的。在本研究中,我们通过 P 位取代和 C 位配位反应成功合成了 FA 固定化 HA 纳米粒子,并将其命名为取代型和配位型。在置换型反应中,当 FA 与 HA 在成核阶段发生反应时,随着 FA 覆盖比表面积的增加,HA 的 PO43- 离子减少,结晶相由缺钙 HA 显著转变为碳化 HA 相;在配位型反应中,当 FA 与 HA 在成核阶段发生反应时,随着 FA 覆盖比表面积的增加,HA 的 PO43- 离子减少,结晶相由缺钙 HA 显著转变为碳化 HA 相。由此可见,FA 是通过 P 位取代的方式固定在 HA 上的。在配位型中,由于 FA 是在晶体生长完成后才与 HA 发生反应的,因此随着 FA 覆盖表面积比率的增加,结晶相也发生了轻微变化,这表明 FA 是通过 C 位配位固定在 HA 上的。由此可见,在合成过程中,我们通过P位取代和C位配位来控制FA在HA纳米粒子上的固定状态。由于 FA 中的 -COO- 离子可选择性地与 HA 中的 P 位点置换,从而使外来有机分子与 HA 中的 Ca2+ 离子直接配位成为可能。因此,本研究的固定化技术有望在一个纳米粒子上实现两种不同药物分子的诊断和治疗功能(即治疗学)。
期刊介绍:
ACS Biomaterials Science & Engineering is the leading journal in the field of biomaterials, serving as an international forum for publishing cutting-edge research and innovative ideas on a broad range of topics:
Applications and Health – implantable tissues and devices, prosthesis, health risks, toxicology
Bio-interactions and Bio-compatibility – material-biology interactions, chemical/morphological/structural communication, mechanobiology, signaling and biological responses, immuno-engineering, calcification, coatings, corrosion and degradation of biomaterials and devices, biophysical regulation of cell functions
Characterization, Synthesis, and Modification – new biomaterials, bioinspired and biomimetic approaches to biomaterials, exploiting structural hierarchy and architectural control, combinatorial strategies for biomaterials discovery, genetic biomaterials design, synthetic biology, new composite systems, bionics, polymer synthesis
Controlled Release and Delivery Systems – biomaterial-based drug and gene delivery, bio-responsive delivery of regulatory molecules, pharmaceutical engineering
Healthcare Advances – clinical translation, regulatory issues, patient safety, emerging trends
Imaging and Diagnostics – imaging agents and probes, theranostics, biosensors, monitoring
Manufacturing and Technology – 3D printing, inks, organ-on-a-chip, bioreactor/perfusion systems, microdevices, BioMEMS, optics and electronics interfaces with biomaterials, systems integration
Modeling and Informatics Tools – scaling methods to guide biomaterial design, predictive algorithms for structure-function, biomechanics, integrating bioinformatics with biomaterials discovery, metabolomics in the context of biomaterials
Tissue Engineering and Regenerative Medicine – basic and applied studies, cell therapies, scaffolds, vascularization, bioartificial organs, transplantation and functionality, cellular agriculture