Matulionyte Marija, Dapkute Dominyka, Budenaite Laima, Jarockyte Greta, Rotomskis Ricardas
Biomedical Physics Laboratory, National Cancer Institute, P. Baublio st. 3b, Vilnius LT-08406, Lithuania.
Biophotonics Group of Laser Research Centre, Vilnius University, Sauletekio ave. 9, Vilnius LT-10222, Lithuania.
Int J Mol Sci. 2017 Feb 10;18(2):378. doi: 10.3390/ijms18020378.
In recent years, photoluminescent gold nanoclusters have attracted considerable interest in both fundamental biomedical research and practical applications. Due to their ultrasmall size, unique molecule-like optical properties, and facile synthesis gold nanoclusters have been considered very promising photoluminescent agents for biosensing, bioimaging, and targeted therapy. Yet, interaction of such ultra-small nanoclusters with cells and other biological objects remains poorly understood. Therefore, the assessment of the biocompatibility and potential toxicity of gold nanoclusters is of major importance before their clinical application. In this study, the cellular uptake, cytotoxicity, and intracellular generation of reactive oxygen species (ROS) of bovine serum albumin-encapsulated (BSA-Au NCs) and 2-(N-morpholino) ethanesulfonic acid (MES)capped photoluminescent gold nanoclusters (Au-MES NCs) were investigated. The results showed that BSA-Au NCs accumulate in cells in a similar manner as BSA alone, indicating an endocytotic uptake mechanism while ultrasmall Au-MES NCs were distributed homogeneously throughout the whole cell volume including cell nucleus. The cytotoxicity of BSA-Au NCs was negligible, demonstrating good biocompatibility of such BSA-protected Au NCs. In contrast, possibly due to ultrasmall size and thin coating layer, Au-MES NCs exhibited exposure time-dependent high cytotoxicity and higher reactivity which led to highly increased generation of reactive oxygen species. The results demonstrate the importance of the coating layer to biocompatibility and toxicity of ultrasmall photoluminescent gold nanoclusters.
近年来，光致发光金纳米团簇在基础生物医学研究和实际应用中都引起了相当大的关注。由于其超小尺寸、独特的类分子光学性质以及易于合成，金纳米团簇被认为是用于生物传感、生物成像和靶向治疗的非常有前景的光致发光剂。然而，这种超小纳米团簇与细胞及其他生物物体的相互作用仍知之甚少。因此，在金纳米团簇临床应用之前，评估其生物相容性和潜在毒性至关重要。在本研究中，对牛血清白蛋白包裹的（BSA-Au NCs）和2-（N-吗啉代）乙磺酸（MES）包覆的光致发光金纳米团簇（Au-MES NCs）的细胞摄取、细胞毒性以及细胞内活性氧（ROS）的产生进行了研究。结果表明，BSA-Au NCs在细胞中的积累方式与单独的BSA相似，表明其通过内吞作用摄取，而超小的Au-MES NCs均匀分布于整个细胞体积包括细胞核中。BSA-Au NCs的细胞毒性可忽略不计，表明这种BSA保护的金纳米团簇具有良好的生物相容性。相比之下，可能由于尺寸超小和涂层较薄，Au-MES NCs表现出与暴露时间相关的高细胞毒性和更高的反应活性，这导致活性氧的产生大幅增加。结果证明了涂层对超小光致发光金纳米团簇生物相容性和毒性的重要性。
