胶体粒子的机械性能调控及其在药物递送中的应用

doi:10.6023/A22010042

化学学报 ›› 2022, Vol. 80 ›› Issue (7): 1010-1020.DOI: 10.6023/A22010042 上一篇下一篇

综述

胶体粒子的机械性能调控及其在药物递送中的应用

高至亮, 李梦琦, 郝京诚, 崔基炜^*()

山东大学胶体与界面化学教育部重点实验室济南 250100

投稿日期:2022-01-22 发布日期:2022-05-20
通讯作者: 崔基炜

作者简介:

高至亮, 博士, 2020年博士毕业于山东大学胶体与界面化学教育部重点实验室, 主要从事功能性生物高分子材料的合成、组装、物理化学性质调控及在生物医学领域的应用研究.

李梦琦, 山东大学胶体与界面化学教育部重点实验室硕博连读研究生, 研究方向为胶体粒子的可控制备、性能调控及其在生物领域中的应用.

郝京诚, 教授, 博士生导师. 1995 年博士毕业于中国科学院兰州化学物理研究所, 1997~2003 年分别在日本、德国和美国从事博士后研究, 主要研究方向是胶体与界面化学及其相关应用.

崔基炜, 教授, 博士生导师. 2010 年博士毕业于山东大学胶体与界面化学教育部重点实验室, 2010 至2016 年在墨尔本大学从事博士后研究工作. 研究领域主要包括高分子胶体、界面组装与调控、药物和疫苗递送等.

基金资助:
国家自然科学基金(21872085); 国家自然科学基金(22102088); 山东省自然科学基金(ZR202102240400)

Tuning the Mechanical Properties of Colloid Particles for Drug Delivery

Zhiliang Gao, Mengqi Li, Jingcheng Hao, Jiwei Cui()

Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, Shandong University, Jinan 250100

Received:2022-01-22 Published:2022-05-20
Contact: Jiwei Cui
Supported by:
National Natural Science Foundation of China(21872085); National Natural Science Foundation of China(22102088); Natural Science Foundation of Shandong Province(ZR202102240400)

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摘要/Abstract

胶体粒子是肿瘤治疗中最常用的载体, 尽管在过去的研究中不同的胶体粒子已经被广泛报道, 但如何进一步提高胶体粒子的药物递送效率仍然存在着一些挑战. 大量的研究表明胶体粒子的尺寸、形状、结构和表面化学等物理化学性质在药物递送过程中具有重要的作用, 但胶体粒子的机械性能对药物递送过程的影响研究和综述相对较少. 本综述从不同机械性能胶体粒子的制备与表征出发, 概述了胶体粒子的机械性能对血液循环、肿瘤富集、渗透以及细胞内化过程的影响, 并对该领域存在的问题以及发展的趋势进行了展望. 该综述有助于帮助科学工作者更好地理解胶体粒子的机械性能对药物递送的影响规律, 从而优化胶体粒子的设计并提高纳米药物的递送效率和生物利用率.

关键词: 胶体粒子, 机械性能, 纳米-生物相互作用, 药物递送, 纳米载体

Colloidal particles are the most common carriers of anticancer drugs. Although various colloidal particles as carriers have been reported, it is still challenging to enhance the drug delivery efficacy. It has been proved that physicochemical properties (e.g., size, shape, structure, and surface chemistry) of colloidal particles play an important role in drug delivery processes, while the influence of the mechanical property of colloidal particles on the drug delivery process is rarely reported and reviewed. In this review, we summarize the preparation and characterization of colloidal particles with different mechanical properties. The influence of the mechanical properties of colloidal particles on blood circulation, tumor accumulation and penetration as well as cell internalization are also highlighted. Furthermore, the challenges and future directions in this field are discussed, which is helpful to understand the influence of mechanical property on the design of colloidal particles as carriers to improve the drug delivery efficacy and bioavailability of nanomedicines.

Key words: colloid particle, mechanical property, bio-nano interaction, drug delivery, nanocarrier

引用此文

高至亮, 李梦琦, 郝京诚, 崔基炜. 胶体粒子的机械性能调控及其在药物递送中的应用[J]. 化学学报, 2022, 80(7): 1010-1020.

Zhiliang Gao, Mengqi Li, Jingcheng Hao, Jiwei Cui. Tuning the Mechanical Properties of Colloid Particles for Drug Delivery[J]. Acta Chimica Sinica, 2022, 80(7): 1010-1020.

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图/表 8

图1. 不同硬度的胶体粒子示意图. (a)水凝胶胶体粒子, (b)纳米胶囊和(c)脂质体胶体粒子

Figure 1. Schematic illustration of (a) hydrogel nanoparticles (NPs), (b) nanocapsules and (c) liposome NPs with different stiffness

图2. (a)介孔硅模板法制备聚谷氨酸-CpG寡脱氧核苷酸(PGA-CpG)胶体粒子示意图; (b) PGA-CpG聚合物化学结构图; (c)不同交联程度的PGA-CpG胶体粒子杨氏模量结果; (d)不同交联程度的PGA-CpG胶体粒子荧光显微镜照片和透射电子显微镜照片[33]

Figure 2. (a) Schematic illustration of the preparation of PGA-CpG particles via templating MS particles; (b) molecular structure of PGA-CpG; (c) Young’s modulus of PGA-CpG particles as a function of cross-linker concentration; (d) fluorescence microscopy and TEM images of the PGA-CpG particles[33]

图3. (a) PLGA磷脂核壳胶体粒子示意图; (b) Lip-F1275%, PLGA70-Lip-F1275%和PLGA160-Lip-F1275%胶体粒子的冷冻电镜照片; Lip-F1275%, PLGA70-Lip-F1275%和PLGA160-Lip-F1275%胶体粒子的荧光强度(c)和杨氏模量(d)结果(n=3); (e) Lip-F1275%, PLGA70-Lip-F1275%和PLGA160-Lip-F1275%胶体粒子的AFM图及施加不同力之后相应的变形图[55]

Figure 3. (a) A schematic diagram of a core-shell PLGA-lipid NP; (b) cryo-TEM images of a Lip-F1275% NP (left), a PLGA70-Lip-F1275% NP (middle), and a PLGA160-Lip-F1275% NP (right), scale bar: 100 nm; (c) fluorescence intensity and (d) Young’s modulus values of Lip-F1275%, PLGA70-Lip-F1275%, and PLGA160-Lip-F1275% NPs (n=3); (e) AFM images of Lip-F1275% NPs, PLGA70-Lip-F1275% NPs, and PLGA160-Lip-F1275% NPs and the corresponding deformation images of the NPs after being subjected to forces of different magnitudes, scale bar: 200 nm[55]

图4. (a)典型AFM力曲线图; (b) DMT模型计算杨氏模量公式; (c)能量损耗计算公式

Figure 4. (a) A typical force vs. distance profile; (b) formula of Young’s modulus based on DMT model; (c) formula of dissipation energy

图5. (a)硬的聚羧酸甜菜碱(poly(carboxybetaine), pCB)胶体粒子和软的pCB胶体粒子通过微孔的示意图; (b)不同交联度的pCB胶体粒子血液循环时间结果[36]; (c)巨噬细胞内吞不同硬度DPNs的示意图; (d)定量分析单个细胞中不同形状和不同机械性能DPNs的个数[66]; (e)微流控模拟血管示意图; (f)不同交联程度PEG胶体粒子和红细胞通过微流控通道的显微镜照片[34]

Figure 5. (a) Schemes showing hard and soft pCB particles to pass through micro pores; (b) in vivo blood circulation profiles of pCB particles with different cross-linking densities[36]; (c) macrophage internalization of DNPs with different stiffness; (d) quantification of the number of particles internalized per cell for the different DPN geometries and mechanical properties[66]; (e) a microfluidic model mimicking aspects of blood capillaries; (f) microscopy images of particles with different stiffness and RBCs passing through the microfluidic capillaries[34]

图6. (a) DPNs胶体粒子的制备示意图; (b)软的和硬的DPNs杨氏模量分析; (c)肿瘤微脉管中DPN颗粒的富集数据图[37]; (d) RBCMs胶体粒子注射2 h后的生物分布统计结果[38]; (e) 不同硬度pCB胶体粒子注射48 h后的生物分布统计结果[36]

Figure 6. (a) Scheme for the preparation of DPNs; (b) Young's modulus analysis for soft and rigid DPNs; (c) DPN accumulation in the tumor microvasculature[37]; (d) biodistribution of RBCMs 2 h postdosing[38]; (e) biodistribution of pCB NPs with varying stiffness 48 h post injection[36]

图7. (a)机械性能可控的硅胶囊制备过程示意图; (b) TEVS-30 h和EOS-40 h硅胶囊的杨氏模量结果; (c)软的和硬的纳米胶囊在3D肿瘤细胞球中的渗透示意图[45]; (d)低硬度、中等硬度以及高硬度的纳米囊泡在3D肿瘤细胞球中的渗透示意图[52]

Figure 7. (a) Schematic illustration for the synthesis of silica nanocapsules with controllable mechanical property; (b) Young’s moduli of TEVS-30 h and TEOS-40 h silica capsules; (c) schematic illustration showing the penetration of stiff and soft nanocapsules in the 3D tumor spheroids[45]; (d) schematic illustration of the penetration of nanovesicles with low, intermediate and high stiffness in the 3D tumor spheroids[52]

图8. (a) P-L和P-W-L胶体粒子的杨氏模量测试结果; (b) MD模拟刚度影响的细胞内化过程[54]; (c) NLP和NLG杨氏模量测试结果; (d)胶体粒子硬度影响细胞内化方式示意图[56]; (e) Hertz模型计算得到CGNPs胶体粒子的杨氏模量结果; (f) CGNPs与细胞共培养4 h后细胞内化的定量分析结果[83]

Figure 8. (a) Young’s modulus of P-L and P-W-L NPs; (b) MD simulations of rigidity-governed cellular internalization[54]; (c) Young’s moduli of NLP and NLG; (d) cell internalization pathway influenced by particle stiffness[56]; (e) Young’s modulus of CGNPs calculated from Hertz model; (f) intracellular uptake of CGNPs after 4 h incubation[83]

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胶体粒子的机械性能调控及其在药物递送中的应用

Tuning the Mechanical Properties of Colloid Particles for Drug Delivery

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