Microgel translocation through pores under confinement.

Microgel translocation through pores under confinement.
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DOI:
10.1002/anie.200906606
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发表时间:
2010-03-15
影响因子:
16.6
通讯作者:
Lyon, L. Andrew
Lyon, L. Andrew
中科院分区:
化学1区
文献类型:
--
作者:
Hendrickson, Grant R.;Lyon, L. Andrew

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在使用合成生物材料的应用中,如药物输送,[1-4]生物成像,[5,6]和组织工程,[7-11]材料的机械性能代表了一组重要的设计参数。[12]大多数生物材料机械性能的研究都集中在细胞如何与不同刚度的表面相互作用或在其上移动,这是机械传导[7,10,11]和细胞增殖或分化的背景。[8,9]然而,很少有研究调查纳米颗粒在纳米或微生物环境中的机械柔软性的影响。然而,有人提出,纳米颗粒的柔软性可能与吞噬作用或内吞作用等过程有关。[13这表明细胞不仅受到大表面或界面的力学影响,而且还受到单个纳米颗粒的刚性影响。纳米颗粒的体内性能强烈依赖于各种生物过程,包括淋巴引流、内吞作用、外渗和肾过滤。有理由认为,具有刚性尺寸依赖性的任何过程也可能依赖于生物材料的机械柔性。[15]因此,在概述与某些工艺相关的纳米颗粒尺寸限制时,有必要考虑力学。当该过程涉及通过小的、明确的孔时,这可能特别重要,例如在肾过滤中。肾或肾小球过滤是生物材料从体内清除小于500 nm的颗粒的两种途径之一。[12另一种清除途径是通过肝脏的胆汁清除;然而,在纳米医学应用中,由于通常使用的小颗粒尺寸,胆汁清除通常被绕过。[16]因此,肾清除是纳米颗粒排泄的理想机制。该机制需要在40至80 mmHg(0.7至1.5 psi)的压差下通过直径约为8 nm的孔(由内皮间隙定义)。[17-21]显然,对于大多数载体系统,这些品质因数不容易满足,需要将降解性整合到纳米颗粒设计中或严格控制小颗粒尺寸。[22-25]在某些情况下,这些修饰可能会对药物负载/释放、循环时间、细胞摄取和细胞毒性产生负面影响。因此,可能需要开发一种载体系统,其具有排泄的能力而没有额外的设计复杂性。对于硬球系统,如量子点,这意味着严格的粒度限制,[26]这可能会对有效载荷产生负面影响,或者可能导致通过淋巴引流的清除。[27]然而,能够递送大的货物但足够柔性以适合通过小孔的柔软的适形纳米颗粒是潜在的有吸引力的替代方案。这种结构的一个例子是水凝胶胶体(即纳米凝胶或微凝胶),由于其显著的网络柔性,其是可以被显著压缩的纳米颗粒。[28日]
In applications utilizing synthetic biomaterials, such as drug delivery,[1–4] bioimaging,[5, 6] and tissue engineering,[7–11] the material mechanical properties represent an important set of design parameters.[12] Most studies of mechanical properties in biomaterials have focused on how cells interact with or move on surfaces of different rigidity in the context of mechanotransduction [7, 10, 11] and cell proliferation or differentiation.[8, 9] However, few studies have investigated the effects of the mechanical softness of nanoparticles in nano-or micro-biological environments. It has been suggested, however, that the softness of nanoparticles may be relevant in processes such as phagocytosis or endocytosis.[13, 14] This indicates that not only are cells affected by the mechanics of large surfaces or interfaces, but also by the rigidity of individual nanoparticles. The in vivo performance of nanoparticles is strongly dependent on a variety of biological processes, including, lymphatic drainage, endocytosis, extravasation, and kidney filtration. It stands to reason that any process that has a rigid size dependence may also be dependent on mechanical flexibility of the biomaterial.[15] Therefore, it is necessary to consider mechanics when outlining the nanoparticle size restrictions relevant for certain processes. This might especially be important when the process involves passage through small, well-defined pores, such as in renal filtration.Renal or glomerular filtration is one of two routes of clearance of biomaterials from the body for particles smaller than 500 nm.[12, 15, 16] The other clearance route is biliary clearance through the liver; however, in nanomedicine applications biliary clearance is generally bypassed due to the small particle sizes typically used.[16] Therefore, renal clearance is a desired mechanism of nanoparticle excretion. This mechanism requires passage through approximately 8-nm diameter pores (as defined by endothelial gaps) under a pressure differential of 40 to 80 mmHg (0.7 to 1.5 psi).[17–21] Obviously, for most carrier systems these figures of merit are not easily met and require the integration of degradability into the nanoparticle design or rigorous control over small particle sizes.[22–25] In some cases these modifications may negatively alter drug loading/release, circulation times, cell uptake, and cytotoxicity. Therefore, it may be desirable to develop a carrier system that has the ability to be excreted without additional design complexity. For a hard sphere system, such as quantum dots, this implies a strict particle size limit,[26] which may negatively impact payload or may result in clearance through lymphatic drainage.[27] However, soft conformable nanoparticles that are able to deliver a large cargo yet are flexible enough to fit through small pores are a potentially attractive alternative. One example of such a construct is that of hydrogel colloids (ie nanogels or microgels), which are nanoparticles that can be dramatically compressed, due to their significant network flexibility.[28]
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