The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles.
The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles.
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DOI：
10.2147/ijn.s36111
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发表时间：
2012
影响因子：
8
通讯作者：
Fröhlich E
中科院分区：
文献类型：
--
作者：
Fröhlich E
许多类型的纳米颗粒(NPs)被测试用于医疗产品，特别是在成像和基因和药物输送方面。对于这些应用，细胞摄取通常是先决条件，除了尺寸外，还受表面特性(如疏水性和电荷)的控制。虽然正电荷似乎改善了成像、基因转移和药物传递的效率，但已有报道称此类构建物具有更高的细胞毒性。本文综述了表面电荷在细胞毒性中的作用、对特定细胞靶点的作用、毒性作用模式、细胞摄取和NPs的细胞内定位等方面的研究结果。对血清和细胞间类型差异的影响进行了讨论。与阴离子NPs相比，阳离子NPs导致更明显的质膜完整性破坏，更强的线粒体和溶酶体损伤，以及更多的自噬小体。一般来说，非吞噬细胞摄取阳离子NPs的程度较高，但电荷密度和疏水性同样重要；吞噬细胞优先摄取阴离子NPs。细胞对阳离子和阴离子NPs没有不同的摄取途径，但高摄取率通常与更大的生物效应有关。吞噬细胞和非吞噬细胞对阳离子和阴离子纳米粒摄取的不同偏好可能会影响纳米粒在药物传递和成像方面的有效性和选择性。
Many types of nanoparticles (NPs) are tested for use in medical products, particularly in imaging and gene and drug delivery. For these applications, cellular uptake is usually a prerequisite and is governed in addition to size by surface characteristics such as hydrophobicity and charge. Although positive charge appears to improve the efficacy of imaging, gene transfer, and drug delivery, a higher cytotoxicity of such constructs has been reported. This review summarizes findings on the role of surface charge on cytotoxicity in general, action on specific cellular targets, modes of toxic action, cellular uptake, and intracellular localization of NPs. Effects of serum and intercell type differences are addressed. Cationic NPs cause more pronounced disruption of plasma-membrane integrity, stronger mitochondrial and lysosomal damage, and a higher number of autophagosomes than anionic NPs. In general, nonphagocytic cells ingest cationic NPs to a higher extent, but charge density and hydrophobicity are equally important; phagocytic cells preferentially take up anionic NPs. Cells do not use different uptake routes for cationic and anionic NPs, but high uptake rates are usually linked to greater biological effects. The different uptake preferences of phagocytic and nonphagocytic cells for cationic and anionic NPs may influence the efficacy and selectivity of NPs for drug delivery and imaging.