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
中科院分区:
文献类型:
--
作者:
Hendrickson, Grant R.;Lyon, L. Andrew
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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DOI:
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发表时间:
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影响因子:
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DOI:
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发表时间:
2004-09-13
期刊:
The Journal of cell biology
影响因子:
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通讯作者:
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DOI:
10.1152/ajprenal.00097.2007
发表时间:
2007-10-01
影响因子:
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作者:
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