研究与开发杂志
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国际标准期刊号: 2311-3278
国际标准期刊号: 2311-3278
尼古拉·达尔多索
多孔硅（pSi）是通过对晶体硅片进行电化学蚀刻而产生的光致发光材料。它适合纳米医学应用，因为它具有惰性、可生物降解、生物相容性并且没有免疫反应。此外，由于量子限制效应，它们的光学特性在生物成像应用方面非常有趣。pSi微粒在纳米医学中的应用的主要问题之一是水环境中光学性质的快速猝灭。我们之前通过壳聚糖和 PEG 等聚合物的共价连接证明了长期光学稳定性。在这项工作中，我们研究了生物缓冲液中微粒的光学性质稳定性（例如，PBS）通过在旋转反应器中通过 ALD（原子层沉积）沉积无机 TiO2 层。该工艺允许沉积具有微调厚度的均匀层。通过优化 ALD 参数，我们使 pSi 微粒子的光学性能稳定了三个多月（截至目前）。我们通过体外测试研究了 pSi-TiO2 微粒对人树突状细胞 (DC) 的影响，发现树突状细胞的活力没有降低，但考虑到纳米医学应用，它们能够通过其他方法增加免疫细胞的激活。必须考虑激动剂。这些结果及其在水溶液中证明的光致发光稳定性使 pSi-TiO2 微粒有机会成为纳米医学应用的有希望的候选者。该工艺允许沉积具有微调厚度的均匀层。通过优化 ALD 参数，我们使 pSi 微粒子的光学性能稳定了三个多月（截至目前）。我们通过体外测试研究了 pSi-TiO2 微粒对人树突状细胞 (DC) 的影响，发现树突状细胞的活力没有降低，但考虑到纳米医学应用，它们能够通过其他方法增加免疫细胞的激活。必须考虑激动剂。这些结果及其在水溶液中证明的光致发光稳定性使 pSi-TiO2 微粒有机会成为纳米医学应用的有希望的候选者。该工艺允许沉积具有微调厚度的均匀层。通过优化 ALD 参数，我们使 pSi 微粒子的光学性能稳定了三个多月（截至目前）。我们通过体外测试研究了 pSi-TiO2 微粒对人树突状细胞 (DC) 的影响，发现树突状细胞的活力没有降低，但考虑到纳米医学应用，它们能够通过其他方法增加免疫细胞的激活。必须考虑激动剂。这些结果及其在水溶液中证明的光致发光稳定性使 pSi-TiO2 微粒有机会成为纳米医学应用的有希望的候选者。我们通过体外测试研究了 pSi-TiO2 微粒对人树突状细胞 (DC) 的影响，发现树突状细胞的活力没有降低，但考虑到纳米医学应用，它们能够通过其他方法增加免疫细胞的激活。必须考虑激动剂。这些结果及其在水溶液中证明的光致发光稳定性使 pSi-TiO2 微粒有机会成为纳米医学应用的有希望的候选者。我们通过体外测试研究了 pSi-TiO2 微粒对人树突状细胞 (DC) 的影响，发现树突状细胞的活力没有降低，但考虑到纳米医学应用，它们能够通过其他方法增加免疫细胞的激活。必须考虑激动剂。这些结果及其在水溶液中证明的光致发光稳定性使 pSi-TiO2 微粒有机会成为纳米医学应用的有希望的候选者。
Nanomaterials that will circulate in the body have great potential for the diagnosis and treatment of diseases. For such applications, it is important that nanomaterials are safely eliminated from the body within a reasonable period of time after they perform their diagnostic or therapeutic functions. Despite efforts to increase their targeting efficiency, the mononuclear phagocytic system cleans significant amounts of systemically introduced nanomaterials before finding their targets, which increases the likelihood of unintentional acute or chronic toxicityHowever, there has been little effort to design the self-destruction of wandering nanoparticles in non-toxic and systemically eliminated products. Here, we present luminescent porous silicon nanoparticles (LPSiNPs) that will carry a payload of drugs and whose intrinsic near-infrared photoluminescence allows monitoring both of accumulation and degradation in vivo. Furthermore, in contrast to most optically active nanomaterials (carbon nanotubes, gold nanoparticles and quantum dots), LPSiNPs self-destruct during the mouse model into renal-purified components for a relatively short period of time with no evidence of toxicity. As a preliminary in vivo application, it demonstrates tumor imaging using dextran-coated LPSiNPs (D-LPSiNPs). These results demonstrate the replacement of a multifunctional low toxicity degradation nanostructure for in vivo applications.
Nanostructured materials have become promising candidates for drug delivery, especially for cancer treatment1. in addition to traditional drug delivery systems based on polymers and lipids (DDS) and other inorganic nanomaterials 2,3,4,5 porous Si (pSi) is a beautiful material for applications in nanomedicine due to its unusual properties, such as a huge area (up to 800 m2 · g - 1) 6, biocompatibility7,8,9 and biodegradability 10,11,12 while maintaining the bioactivity of the drug13. moreover, the nanostructured pSi showed unique optical14 and luminescent properties11,15, which are favorable for the self-declaration of the load and the release of drugs. The pSis are often manufactured in films 6,16,17,18,19,20, microparticles 21,22,23 or nanoparticles 11,24,25,26,27. The loading capacities of the drugs and the release kinetics depend strongly on the area and the surface chemistry of the materials pSi28,29. And not surprisingly, hydrophobic preparations are more efficiently loaded into hydrophobic pores 17.28. However, often when used under physiological conditions, drug reservoirs are often difficult to moisten with hydrophobic exterior surfaces. Thus, pSi decorations on the inner and outer surfaces with various properties are very popular.
A selective modification on the external surfaces of pSi was reported for the first time by Cunin and his colleagues31. Here, the flat silicon was thermosilylated thermally with hydrocarbons, followed by an electrochemical etching. The organic layer remained at least partially on the outer surface while fresh pores were presented, leaving the inner surfaces available for further modification. For inner surface modification, several anodization and silanization cycles were applied on alumina membranes, leading to spatially controlled surface modifications32,33. Kilian et al. presented a differential functionalization on exterior and interior pSi surfaces which relied on the mixture of physical phenomenon and capillarity30, the entire surface was first modified with hydrophobic 10-succinimidylundecenoate which could effectively repel water from penetrating the internal pores, leading to peptide conjugation occurring only on the external surfaces. On the other hand, using organic solvents, various reagents were attached to the internal surfaces of pSi. In the same way, Wu and Sailor used an inert fluid as a "mask" to protect the internal pores from exposure to the acid solution during the selective functionalization of the external surface of pSi34. A three-step functionalization procedure has recently been described, consisting of two hydrosilylation reactions separated by selective digestion of the outer surface. This procedure provides the outer surface of pSi with hydrophilic groups, limiting hydrophobization to the inner pore walls, as demonstrated by angular resolution X-ray spectroscopy (XPS) using pSi35 macropores. A less dependent pore size procedure was also reported in which the hydrosilylation reaction using light resulted in discrete surface chemistry of the pSi layers, where the depth of the chemical modification depends on the wavelength of sunlight used in the procedure36. However, pSi exterior surface modification with polymers, especially anti-fouling polymers, while decorating interior pore walls with hydrophobic species has not been demonstrated thus far.
Si 片晶购自法国 Siltronix。除非另有说明，用于合成的所有化学品（试剂和溶剂）均购自 Sigma-Aldrich，具有最佳可用纯度，并按指示使用。对于铕测试，DELFIA 增强溶液和 100 nM 欧洲标准品等试剂购自澳大利亚 PerkinElmer。人白蛋白（HSA，99%）和纤连蛋白（FN）购自 Sigma-Aldrich。细胞培养使用以下试剂：多聚甲醛（Sigma）、DMEM培养基（Invitrogen）、胎牛血清（FBS，Invitrogen）、Triton™ X-100（Sigma）和4’，6-二脒基-2-苯基吲哚（DAPI） ）（Invitrogen）并且全部按收到时使用。小鼠L929成纤维细胞用于细胞培养实验。
用于药物输送的智能纳米转运体等无机结构结合了无机药物输送结构的最新研究。详细介绍和讨论了各种类型的纳米载体，提供了无机纳米颗粒在药物应用中的现代概述。本书由多位国际科学家撰写，对于生物材料、制药领域的研究人员以及想要更多了解无机智能纳米载体当前应用的人们来说可能是有价值的参考。
注：这项工作部分在 2017 年 11 月 23 日至 24 日在澳大利亚墨尔本举行的第 17 届纳米医学和医疗保健纳米技术国际会议和展览会上展出。