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通过高灵敏度单光子发射计算机断层扫描(SPECT)探测稳定球形和丝状胶束的体内生物分布。

In vivo biodistribution of stable spherical and filamentous micelles probed by high-sensitivity SPECT.

作者信息

Jennings L, Ivashchenko O, Marsman I J C, Laan A C, Denkova A G, Waton G, Beekman F J, Schosseler F, Mendes E

机构信息

Institut Charles Sadron (CNRS), University of Strasbourg, Strasbourg, France.

出版信息

Biomater Sci. 2016 Aug 19;4(8):1202-11. doi: 10.1039/c6bm00297h. Epub 2016 Jun 10.

DOI:10.1039/c6bm00297h
PMID:27286085
Abstract

Understanding how nanoparticle properties such as size, morphology and rigidity influence their circulation time and biodistribution is essential for the development of nanomedicine therapies. Herein we assess the influence of morphology on cellular internalization, in vivo biodistribution and circulation time of nanocarriers using polystyrene-b-poly(ethylene oxide) micelles of spherical or elongated morphology. The glassy nature of polystyrene guarantees the morphological stability of the carriers in vivo and by encapsulating Indium-111 in their core, an assessment of the longitudinal in vivo biodistribution of the particles in healthy mice is performed with single photon emission computed tomography imaging. Our results show prolonged blood circulation, longer than 24 hours, for all micelle morphologies studied. Dynamics of micelle accumulation in the liver and other organs of the reticuloendothelial system show a size-dependent nature and late stage liver clearance is observed for the elongated morphology. Apparent contradictions between recent similar studies can be resolved by considering the effects of flexibility and degradation of the elongated micelles on their circulation time and biodistribution.

摘要

了解纳米颗粒的性质(如尺寸、形态和刚性)如何影响其循环时间和生物分布对于纳米医学疗法的发展至关重要。在此,我们使用球形或细长形态的聚苯乙烯-b-聚(环氧乙烷)胶束评估形态对纳米载体的细胞内化、体内生物分布和循环时间的影响。聚苯乙烯的玻璃态性质保证了载体在体内的形态稳定性,并且通过将铟-111包裹在其核心中,利用单光子发射计算机断层扫描成像对健康小鼠体内颗粒的纵向生物分布进行评估。我们的结果表明,所研究的所有胶束形态的血液循环时间都延长了,超过24小时。胶束在肝脏和网状内皮系统其他器官中的积累动态显示出尺寸依赖性,并且观察到细长形态的胶束在后期肝脏清除。通过考虑细长胶束的柔韧性和降解对其循环时间和生物分布的影响,可以解决近期类似研究之间明显的矛盾。

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