定量仿真研究贵金属纳米探针聚集诱导的非线性增强光热效应
Photothermal therapy is a tumor treatment method that converts optical energy into thermal energy, kills tumor cells via local heating, and triggers biochemical processes. A necessary condition for the development of photothermal therapy is to obtain a highly efficient probe for photothermal conversion with satisfactory safety and targeting. The use of nanoprobes coupled by local surface plasmon resonance is one of the latest research and development directions in photothermal therapy. Because local surface plasmon resonance significantly depends on specific nanostructures, the position of the extinction peak is adjusted to locate in the optical window of biological tissues, and the extinction intensity is adjusted to achieve appropriate photothermal conversion efficiency, which can be theoretically achieved through the morphological design of nanoprobes. However, it remains challenging to design these nanoprobes under quantitative guidance. In this study, we systematically investigated and quantitatively analyzed the nonlinear optical field and photothermal enhancement effect produced using the local surface plasmon resonance coupling effect and their mechanisms caused by various factors. This approach provides systematic and comprehensive theoretical guidance for designing efficient plasma nanoaggregation probes.
In this study, the nonlinear optical and photothermal effects induced by the aggregation of noble metal nanoprobes were quantitatively demonstrated using finite element simulations. In each simulation experiment, nanoprobes with different degrees of aggregation, gap distances, particle sizes, shapes, permutations, and materials of nanoparticles were constructed to evaluate the influence of these factors on the aggregation enhancement effect and photothermal conversion efficiency. For the degree of aggregation, isolated gold nanospheres, regular-triangular gold nanosphere trimers, and hexagonal gold nanosphere heptamers were used as examples. For the gap distance, we quantitatively simulated gold nanosphere heptamers with gap distances of 0.5, 1, and 2 nm. For the particle size, simulated gold nanosphere heptamers with spherical diameters of 15, 30, and 60 nm were used. For the particle shape, simulated gold nanoheptamers with spheres, hexagonal prisms, and cubes were used. For permutations, simulated heptamers, rings, and chains were used. Gold and platinum were compared.
Self-assembly of nanoparticles has been a prominent topic in science and technology. Under the guidance of theory, the reasonable design and construction of nanocomponents can effectively promote their applications in photothermal therapy and other fields. In this study, noble metal nanoprobes with a specific nanocoupling structure were constructed to demonstrate the photothermal effect of nonlinear enhancement induced by aggregation. The essence of enhanced local surface plasmon resonance coupling is that, after the external electric field excites the nanounit into an electric dipole, the electric field excited by the dipole acts on other nearby dipoles. Therefore, the key to designing a high photothermal conversion efficiency is to make the dipole as strong as possible in an electric field excited by other dipoles. The simulation experiment demonstrated that a reasonable design of the degree of aggregation, gap distance, particle size, shape, and arrangement is adequate for achieving this goal. Although only two-dimensional coupled nanoprobes are shown, this approach can be easily extended to three-dimensional coupled nanocomponents with increased coupling efficiency, and nonlinear enhanced photothermal effects can be expected.
We quantitatively simulated the nonlinear enhanced photothermal effect of local surface plasmon resonance-coupled noble metal nanoprobes. Instead of isolated nanoparticles, a large number of nanoparticles gather in space and form a specific nanocoupling structure. The strong optical and thermal coupling between the nanoparticles results in an enhancement of the weighted optical absorption of each particle by several times and the corresponding thermal field enhancement. The dependence of the nonlinear photothermal enhancement effect on the aggregation quantity is discussed quantitatively. Moreover, the effects of the gap distance, particle size, shape, and arrangement mode on the photothermal conversion efficiency of the nanoprobe were discussed extensively. The photothermal nonlinear enhancement mechanism based on the plasmon resonance coupling mechanism is widely applicable to various precious metal nanomaterials. Based on finite element analysis, simulations were conducted, and the simulation results reflected the theoretical discussion satisfactorily. This study paves the way for the rational design and optimization of noble metal nanoprobes with higher light absorption and photothermal conversion efficiency.
1 引言
光热疗法是一种将光能转变为热能,通过局部加热并触发生化过程来杀死肿瘤细胞的肿瘤治疗方法[1]。寻找一种光热转换效率高且具有足够安全性、靶向性的探针,是光热疗法开展的基础。同时,这样的探针也可作为光热源用于热声、光声成像等研究领域[2-4],甚至可被用于多模态成像治疗一体化研究[5]。在过去的几十年间,尺寸小于光波长的金属纳米颗粒已被广泛应用于光伏发电、光学传感和生物医学等领域[6-12],这是由于其在外部光照射下可以产生局域表面等离子体共振。在尺寸适当的纳米颗粒中,受限的自由电子以与入射光波相同的频率振荡,并最终进入共振,产生强烈的、高度局域化的电磁场[13],因而可观察到明显的消光现象。纳米颗粒吸收的光能可以通过非辐射损耗转化为热。由于局域表面等离子体共振强烈地依赖于具体的纳米结构,因此,调整消光峰的位置使之处于生物组织的光学窗口,或者调节消光强度使其具有合适的光热转换效率,理论上都可以通过对纳米探针进行形态学设计实现。由于调节孤立的单个纳米粒子与激发光的相互作用以及进一步改善其光学和热学性能的能力有限,因此,由多个纳米粒子聚集或自组装而成的纳米探针成为了研究热点[14-15]。当颗粒间的距离小于或等于纳米颗粒的尺寸时,颗粒间复杂的相互作用会引起等离子激元耦合[16],使纳米探针表现出丰富多样的新颖的非线性效应,进而使其在光学和热响应方面与它们的个体完全不同,因而具有更大的生物应用潜力。因此,基于局域表面等离子体共振耦合的贵金属纳米探针是新一代光热转换剂的热点研究和发展方向之一。
尽管相关研究已经证明了金纳米囊泡[17]、纳米多触手[18]、纳米枝状壳层[19]、纳米团簇[20]等纳米聚合体的实验应用,但目前仍缺乏相关定量研究。定量分析纳米颗粒聚集程度和形态对光热效率的影响,最大化获取纳米组件的耦合效应以提高操纵其光学性能和相应热学性能的能力,对于更加合理、有指导性地设计、构建和优化高效的等离子体纳米探针具有重要意义。本课题组利用有限元仿真定量演示了贵金属纳米探针聚集诱导的非线性光学及光热效应,获得了定量的温度场分布。进一步,本文基于纳米粒子的材质、尺寸、排列方式等探讨了纳米探针的光热转换效率,同时对局域表面等离子体共振耦合效应产生的非线性光场、光热增强效应及其机制进行了深入定量分析,以期为设计更高效的等离子体纳米聚集探针提供系统和较为全面的理论指导。
2 基本原理与实验仿真
贵金属纳米探针的基于局域表面等离子体共振原理的强烈的光吸收,以及后续由无辐射跃迁热能释放引起的热过程,在生物学和生物医学领域有着广泛应用和重要意义。照射探针的高强度激光与贵金属纳米探针之间的相互作用涉及多个时空尺度的物理过程,其中严格的理论分析需要包含量子和连续能级理论的多尺度分析。为了简化问题,本文认为连续能级理论可以用于研究贵金属纳米探针的光吸收以及之后的热过程。
贵金属纳米探针的光吸收来源于孤立的单个纳米粒子的表面等离子体共振吸收以及纳米探针聚集引起的极强的粒子间耦合效应。后者是非线性光热增强效应的来源。当几何尺寸远小于光波长的纳米探针被强烈的激光照射时,纳米探针的电子云概率场会受到电磁场的扰动,从而偏离原先的平衡位置,发生来回振荡。假设贵金属纳米探针被一束激光照射(暂不考虑磁场的影响),该光可认为是频率为ω、电场强度为
式中:
式中:
式中:
式中:
电偶极子之间的相互作用非常复杂,很难得到解析解。本文将基于有限元的计算方法作为定量技术,研究以局域表面等离子体共振为媒介的电场耦合和光吸收增强。为了系统地理解每个孤立纳米颗粒之间的共振耦合及其对光吸收的贡献,本文研究了三种基本耦合纳米结构,即孤立金纳米球、正三角形金纳米球三聚体和密排六边形金纳米球七聚体。单个金纳米球的直径(D)设置为15 nm,粒子间距离(d)设置为1 nm。入射激光平行于由箭头指示的轴偏振方向,如
式中:
图 1. 光热转换仿真。(a)~(c)孤立金纳米球、正三角形金纳米球三聚体和密排六边形金纳米球七聚体探针的局域表面等离子体共振电场增强;(d)不同耦合纳米结构纳米探针的光热功率谱仿真结果;(e)不同耦合纳米结构纳米探针中每个金纳米球的最大热功率
Fig. 1. Simulation of photothermal conversion. (a)-(c) Localized surface plasmon resonance induced electric field enhancement of nanoprobe with single gold nanosphere, equilateral trangular gold nanosphere trimer, and densely packed hexagonal gold nanosphere heptamer, respectively; (d) simulated optical heat power of nanoprobe with different coupling nanostructures; (e) simulated maximum optical heat power per nanosphere in nanoprobe with different coupling nanostructures
纳米探针将吸收的激光能量转换为热,纳米探针成为热源,导致局部升温以及以其为中心的热扩散,温度场可以通过热扩散方程来描述,即
式中:
为了进一步证明纳米探针的非线性增强光热效应,本文分别定量模拟了经激光照射一定时间后上述三种探针及其周围环境的温度场。在仿真中,设置纳米探针与周围环境的初始温度均为297.1 K,纳米探针在电场强度为4×105 V/m的激光下照射10 ns。
图 2. 热扩散仿真。(a)~(c)孤立金纳米球、正三角形金纳米球三聚体和密排六边形金纳米球七聚体探针经电场强度为4×105 V/m的激光照射10 ns后的定量仿真温度场;(d)虚线处的温度分布;(e)不同耦合纳米结构纳米探针经激光照射10 ns后的最高温度
Fig. 2. Simulation of thermal diffusion. (a)-(c) Simulated quantitative temperature fields of nanoprobe with single gold nanosphere, equilateral trangular gold nanosphere trimer, and densely packed hexagonal gold nanosphere heptamer after irradiation for 10 ns by laser with electric field intensity of 4×105 V/m; (d) temperature distribution along the dotted lines in figures (a)-(c); (e) maximum temperature of nanoprobes with different coupling nanostructures after irradiation for 10 ns by laser
在相同的激光照射下,与其他耦合纳米结构相比,纳米球七聚体探针表现出更显著的温度升高。出现这种现象的原因主要有两个方面:1)与其他耦合纳米结构相比,纳米球七聚体探针中每个粒子的光学吸收更强;2)小尺寸效应引起的热从纳米探针扩散到周围环境,随着纳米球数量增加,颗粒间温度场的重叠对非线性局部加热具有显著贡献。
影响贵金属纳米探针电场和热耦合的一个关键因素是等离子体激元个体之间的间隙距离。如式(
图 3. 纳米球间隙d对纳米探针性能的影响。(a)~(c)纳米球间隙分别为2、1、0.5 nm的密排六边形金纳米球七聚体探针的局域表面等离子体共振电场增强;(d)不同纳米球间隙的密排六边形金纳米球七聚体探针的光热功率谱仿真结果;(e)~(g)不同纳米球间隙的密排六边形金纳米球七聚体探针经电场强度为4×105 V/m的激光照射10 ns后的定量仿真温度场;(h)虚线处的温度分布
Fig. 3. Influence of nanosphere-nannosphere gap (d) on nanoprobe performance. (a)-(c) Localized surface plasmon resonance induced electric field enhancement of gold nanosphere heptamer probe with nanosphere-nanosphere gap distance of 2, 1, and 0.5 nm; (d) simulated optical heat power of gold nanosphere heptamer probe with different gaps; (e)-(g) simulated quantitative temperature fields of gold nanosphere heptamer probe with different gaps after irradiation for 10 ns by a laser with electric field intensity of 4×105 V/m; (h) temperature distribution along the dotted lines in figures (e)-(g)
为探讨纳米探针尺寸对聚集增强效应的影响,以金纳米球作为单元,选择密排六边形七聚体展开仿真实验。其中,纳米球的直径分别设定为15、30、60 nm,纳米球之间的间距保持定值(1 nm)。如
图 4. 单球直径对纳米探针性能的影响。(a)~(c)单球直径分别为15、30、60 nm的金纳米球七聚体探针的局域表面等离子体共振电场增强;(d)~(f)不同单球直径的金纳米球七聚体探针经电场强度为4×105 V/m的激光照射10 ns后的定量仿真温度场;(g)不同单球直径的金纳米球七聚体探针的单位体积光热功率谱仿真结果;(h)虚线处的温度分布
Fig. 4. Influence of single-sphere diameter on nanoprobe performance. (a)-(c) Localized surface plasmon resonance induced electric field enhancement of gold nanosphere heptamer probe with single-sphere diameter of 15, 30, and 60 nm; (d)-(f) simulated quantitative temperature fields of gold nanosphere heptamer probe with different single-diameter after irradiation for 10 ns by a laser with electric field intensity of 4×105 V/m; (g) simulated optical heat power per volume of gold nanosphere heptamer probe with different single-sphere diameters; (h) temperature distribution along the dotted lines in figures (d)-(f)
构成单元的形状也是影响局域表面等离子体共振效应的重要因素之一。为此,本文尝试在仿真中使用不同形状的纳米颗粒(即球形、六棱柱与立方体)来构成纳米探针。为了使它们具有可比性,球形单元的直径、六棱柱底面的内接圆直径、六棱柱的高以及立方体的边长均为15 nm,纳米探针的组成方式如
图 5. 颗粒形状对纳米探针性能的影响。(a)~(c)颗粒形状分别为球形、六棱柱、立方体的金纳米七聚体探针的局域表面等离子体共振电场增强;(d)~(f)不同形状颗粒构成的金纳米七聚体探针经电场强度为4×105 V/m的激光照射10 ns后的定量仿真温度场;(g)不同形状颗粒构成的金纳米七聚体探针的单位体积光热功率谱仿真结果;(h)虚线处的温度分布
Fig. 5. Influence of particle shape on nanoprobe performance. (a)-(c) Localized surface plasmon resonance induced electric field enhancement of gold nano heptamers probe with spherical, hexagonal prismatic and cube particles; (d)-(f) simulated quantitative temperature fields of gold nano heptamers probe with different shapes of particles after irradiation for 10 s by a laser with electric field intensity of 4×105 V/m; (g) simulated optical heat power per volume of gold nano heptamers probe with different shapes of particles; (h) temperature distribution along the dotted lines in figures (d)-(f)
在颗粒的大小、形状、数量完全相同的情况下,组装纳米探针的纳米颗粒的排列方式也是影响纳米探针性能的重要因素。在仿真实验中,本文将7个直径为15 nm的金纳米球分别以密排六边形七聚体、环形和长链形组装成纳米探针。需要说明的是,长链的排列方向与入射光的电场偏振方向平行,如
图 6. 排列方式对纳米探针性能的影响。(a)~(c)纳米颗粒以密排六边形七聚体、环形和长链组成的纳米探针的局域表面等离子体共振电场增强;(d)不同排列方式下纳米探针的光热功率谱仿真结果;(e)~(g)不同排列方式下纳米探针经电场强度为4×105 V/m的激光照射10 ns后的定量仿真温度场;(h)虚线处的温度分布
Fig. 6. Influence of permutation mode on nanoprobe performance. (a)-(c) Localized surface plasmon resonance induced electric field enhancement of nanoprobe constituted by nanoparticles with densely packed hexagonal heptamer, ring shape, and long chain; (d) simulated optical heat power of nanoprobe with different permutation modes; (e)-(g) simulated quantitative temperature fields of gold nanoprobe with different permutation modes after irradiation for 10 ns by a laser with electric field intensity of 4×105 V/m; (h) temperature distribution along the dotted lines in figures (e)-(g)
在设计纳米探针时,材料的选择是必须考虑的一个问题。除黄金外,铂金等其他贵金属也可以作为纳米探针材料。在仿真实验中,本文比较了直径为15 nm的铂纳米球在组成七聚体纳米探针前后的光热转化能力。
图 7. 铂纳米球的聚集增强。(a)铂纳米球的电场分布;(b)铂纳米球聚集为七聚体后的电场耦合增强;(c)铂纳米球聚集为七聚体前后每个纳米球的光热功率谱仿真结果;(d)金纳米球与铂纳米球聚集为七聚体后每个纳米球光热功率提升百分比
Fig. 7. Aggregation enhancement of platinum nanospheres. (a) Electric field distribution of platinum nanosphere; (b) electric field enhancement for platinum nanospheres after aggregation into heptamer; (c) simulated optical heat power per platinum nanospheres before and after aggregation into heptamer; (d) percentage increase of optical heat power per gold or platinum nanosphere after aggregation into heptamer
3 分析与讨论
纳米颗粒的自组装一直是科学和技术领域的热门话题。在理论指导下合理设计和构建纳米组件可以有效促进其在光热治疗及其他领域的应用。本文构建了具有一定纳米耦合结构的贵金属纳米探针,证明了聚集诱导的非线性增强的光热效应。综合分析各种因素的影响后发现,局域表面等离子体共振耦合增强的本质是外电场将纳米单元激发为电偶极子后,偶极子所激发的电场对周围其他偶极子的作用。因此,设计高光热转换效率的关键在于尽量使偶极子处于其他偶极子所激发电场的更强处。仿真实验有力地证明了合理设计颗粒的聚集程度、间隙、尺寸、形状和排列方式是实现目标的有效途径。虽然本文仅显示了二维耦合纳米探针,但该策略可以容易地扩展到具有更高耦合效率的三维耦合纳米组件上,并且可以预期非线性增强的光热效应。不过,在实际生物应用中还应考虑贵金属纳米探针的结构稳定性。
4 结论
本文定量模拟了局域表面等离子体共振耦合贵金属纳米探针的非线性增强光热效应。与孤立纳米颗粒相比,更多的纳米粒子在空间聚集并组成一定的纳米耦合结构后,纳米颗粒之间的强光学和热耦合作用可以实现每个颗粒加权光学吸收的几倍增强以及相应的热场增强。本文定量讨论了非线性光热增强效应对颗粒聚集数量的依赖性,讨论了颗粒间隙、尺寸、形状、排列方式等对纳米探针光热转换效率的影响,证实了以等离子激元共振耦合为机制的光热非线性增强在多种贵金属纳米材料中具有广泛的适用性。基于有限元分析技术展开模拟仿真研究,仿真结果很好地印证了理论分析的正确性。本工作为合理设计具有更高光吸收率与光热转换效率的贵金属纳米探针提供了借鉴。
[1] Chen Q, Wang C, Zhan Z X, et al. Near-infrared dye bound albumin with separated imaging and therapy wavelength channels for imaging-guided photothermal therapy[J]. Biomaterials, 2014, 35(28): 8206-8214.
[2] Li W T, Sun X L, Wang Y, et al. In vivo quantitative photoacoustic microscopy of gold nanostar kinetics in mouse organs[J]. Biomedical Optics Express, 2014, 5(8): 2679-2685.
[3] Peng Y, Liu Y, Lu X L, et al. Ag-hybridized plasmonic Au-triangular nanoplates: highly sensitive photoacoustic/Raman evaluation and improved antibacterial/photothermal combination therapy[J]. Journal of Materials Chemistry B, 2018, 6(18): 2813-2820.
[4] Xu J W, Cheng X J, Chen F X, et al. Fabrication of multifunctional polydopamine-coated gold nanobones for PA/CT imaging and enhanced synergistic chemo-photothermal therapy[J]. Journal of Materials Science & Technology, 2021, 63: 97-105.
[5] Li Y, Liu G H, Ma J Y, et al. Chemotherapeutic drug-photothermal agent co-self-assembling nanoparticles for near-infrared fluorescence and photoacoustic dual-modal imaging-guided chemo-photothermal synergistic therapy[J]. Journal of Controlled Release, 2017, 258: 95-107.
[6] Clavero C. Plasmon-induced hot-electron generation at nanoparticle/metal-oxide interfaces for photovoltaic and photocatalytic devices[J]. Nature Photonics, 2014, 8(2): 95-103.
[7] Ng S M, Koneswaran M, Narayanaswamy R. A review on fluorescent inorganic nanoparticles for optical sensing applications[J]. RSC Advances, 2016, 6(26): 21624-21661.
[8] Wang S S, Chen R H, Yu Q, et al. Near-infrared plasmon-boosted heat/oxygen enrichment for reversing rheumatoid arthritis with metal/semiconductor composites[J]. ACS Applied Materials & Interfaces, 2020, 12(41): 45796-45806.
[9] 徐娅, 边捷, 张伟华. 局域表面等离激元纳米光学传感器的原理与进展[J]. 激光与光电子学进展, 2019, 56(20): 202407.
Xu Y, Bian J, Zhang W H. Principles and processes of nanometric localized-surface-plasmonic optical sensors[J]. Laser&Optoelectronics Progress, 2019, 56(20): 202407.
[10] 陈泓先, 孙宁, 张洁. 泡沫镍耦合金纳米结构增强拉曼散射[J]. 光学学报, 2022, 42(5): 0524001.
[11] 黄向民, 施慧, 赵航, 等. 基于光热效应的纳米塑料捕获和SERS检测[J]. 光学学报, 2022, 42(16): 1624001.
[12] Yang X, Yang M X, Pang B, et al. Gold nanomaterials at work in biomedicine[J]. Chemical Reviews, 2015, 115(19): 10410-10488.
[13] Hutter E, Fendler J H. Exploitation of localized surface plasmon resonance[J]. Advanced Materials, 2004, 16(19): 1685-1706.
[14] Fan J A, Wu C, Bao K, et al. Self-assembled plasmonic nanoparticle clusters[J]. Science, 2010, 328(5982): 1135-1138.
[15] Zheng M B, Yue C X, Ma Y F, et al. Single-step assembly of DOX/ICG loaded lipid: polymer nanoparticles for highly effective chemo-photothermal combination therapy[J]. ACS Nano, 2013, 7(3): 2056-2067.
[16] Rechberger W, Hohenau A, Leitner A, et al. Optical properties of two interacting gold nanoparticles[J]. Optics Communications, 2003, 220(1/2/3): 137-141.
[17] Huang P, Lin J, Li W W, et al. Biodegradable gold nanovesicles with an ultrastrong plasmonic coupling effect for photoacoustic imaging and photothermal therapy[J]. Angewandte Chemie (International Ed. in English), 2013, 52(52): 13958-13964.
[18] Dey P, Tabish T A, Mosca S, et al. Plasmonic nanoassemblies: tentacles beat satellites for boosting broadband NIR plasmon coupling providing a novel candidate for SERS and photothermal therapy[J]. Small, 2020, 16(10): 1906780.
[19] Liu Y P, Zhang X W, Luo L Y, et al. Gold-nanobranched-shell based drug vehicles with ultrahigh photothermal efficiency for chemo-photothermal therapy[J]. Nanomedicine: Nanotechnology, Biology and Medicine, 2019, 18: 303-314.
[20] Li X M, Yu L C, Zhang C N, et al. Tumor acid microenvironment-activated self-targeting & splitting gold nanoassembly for tumor chemo-radiotherapy[J]. Bioactive Materials, 2022, 7: 377-388.
[21] Draine B T, Flatau P J. Discrete-dipole approximation for scattering calculations[J]. Journal of the Optical Society of America A, 1994, 11(4): 1491-1499.
[22] Gunnarsson L, Rindzevicius T, Prikulis J, et al. Confined plasmons in nanofabricated single silver particle pairs: experimental observations of strong interparticle interactions[J]. The Journal of Physical Chemistry B, 2005, 109(3): 1079-1087.
Article Outline
张奇睿, 石玉娇. 定量仿真研究贵金属纳米探针聚集诱导的非线性增强光热效应[J]. 中国激光, 2023, 50(9): 0907201. Qirui Zhang, Yujiao Shi. Quantitative Simulation of Nonlinear Enhanced Photothermal Effect Induced by Aggregation of Noble-Metal Nanoprobe[J]. Chinese Journal of Lasers, 2023, 50(9): 0907201.