超越金纳米颗粒的细胞毒性：损害转移标志的潜力
Beyond gold nanoparticles cytotoxicity: potential to impair metastasis hallmarks
摘要：
本研究旨在研究由阴离子多糖阿拉伯胶（GA-AuNPs）稳定的约3 nm的超小金纳米颗粒（AuNPs）的抗肿瘤作用。重点是使用高转移性黑色素瘤模型下调侵袭性肿瘤的癌症标志。我们首先证明了GA-AuNPs在生物环境下表现出优异的稳定性。通过标准2D体外试验确定了对七种不同细胞系（包括致瘤细胞和非致瘤细胞）的非细胞毒性浓度。低于2.4 mg L-1的金浓度无细胞毒性，因此选择用于进一步分析。暴露于GA-AuNP的细胞通过内吞过程被黑素瘤细胞摄取。接下来，我们使用非细胞毒性浓度的这种纳米材料描述了显着的生物学特性。通过细胞外基质屏障的入侵以及3D生长能力（锚定非依赖性集落形成和球状体生长）受到2.4 mg L-1 GA-AuNP的负面影响。此外，暴露的球状体显示出形态学变化，表明GA-AuNP可以渗透到预先形成的肿瘤中并影响其完整性。总之，这些结果表明，可以通过选择正确的浓度来避免副作用，如细胞毒性，然而，保留了所需的效果，如调节关键的肿瘤细胞恶性特征。
英文摘要：
This study aimed to investigate the antitumor effect of ultrasmall gold nanoparticles (AuNPs), around 3 nm, stabilized by the anionic polysaccharide gum arabic (GA-AuNPs). The focus was downregulation of cancer hallmarks of aggressive tumors, using a highly metastatic model of melanoma. We first demonstrated that GA-AuNPs showed excellent stability under biological environment. Non-cytotoxic concentrations to seven different cell lines, including tumorigenic and non-tumorigenic cells, were determined by standard 2D in vitro assays. Gold concentrations below 2.4 mg L-1 were non-cytotoxic and therefore chosen for further analyses. Cells exposed to GA-AuNPs were uptaken by melanoma cells through endocytic processes. Next, we described remarkable biological properties using non-cytotoxic concentrations of this nanomaterial. Invasion through an extracellular matrix barrier as well as 3D growth capacity (anchorage-independent colony formation and spheroids growth) were negatively affected by 2.4 mg L-1 GA-AuNPs. Additionally, exposed spheroids showed morphological changes, suggesting that GA-AuNPs could penetrate into the preformed tumor and affect its integrity. All together these results demonstrate that side effects, such as cytotoxicity, can be avoided by choosing the right concentration, nevertheless, preserving desirable effects such as modulation of key tumor cell malignancy features.
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