Specific targeting of tumor tissues is essential for tumor imaging and therapeutics but remains challenging. Here, we report an unprecedented method using synthetic sulfonic-graphene quantum dots (sulfonic-GQDs) to exactly target the cancer cell nuclei in vivo without any bio- ligand modification, with no intervention in cells of normal tissues. The key factor for such selectivity is the high interstitial fluid pressure (IFP) in tumor tissues, which allows the penetration of sulfonic-GQDs into the plasma membrane of tumor cells. In vitro, the sulfonic-GQDs are repelled out of the cell membrane because of the repulsive force between negatively charged sulfonic-GQDs and the cell membranes which contributes to the low distribution in normal tissues in vivo. However, the plasma membrane-crossing process can be activated by incubating cells in ultrathin film culture medium because of the attachment of sulfonic-GQDs on cell memebranes. Molecular dynamics simulations demonstrated that, once transported across the plasma membrane, the negatively charged functional groups of these GQDs will leave the membrane with a self-cleaning function retaining a small enough size to achieve penetration through the nuclear membrane into the nucleus. Our study showed that IFP is a previously unrecognized mechanism for specific targeting of tumor cell nuclei and suggested that sulfonic-GQDs may be developed into novel tools for tumor-specific imaging and therapeutics.

中文翻译：

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体内功能化石墨烯量子点的肿瘤细胞特异性核靶向。

肿瘤组织的特异性靶向对于肿瘤成像和治疗是必不可少的，但是仍然具有挑战性。在这里，我们报道了一种空前的方法，该方法使用合成的磺酸-石墨烯量子点（sulfonic-GQDs）在没有任何生物配体修饰的情况下在体内准确靶向癌细胞核，而无需干预正常组织的细胞。这种选择性的关键因素是肿瘤组织中的高组织液压力（IFP），这可使磺酸GQD渗透到肿瘤细胞的质膜中。在体外，由于带负电荷的磺酸-GQD与细胞膜之间的排斥力，磺酸-GQD被排斥出细胞膜，这导致体内正常组织中的分布低。然而，由于磺酸-GQDs附着在细胞膜上，可以通过在超薄膜培养基中孵育细胞来激活质膜穿越过程。分子动力学模拟表明，一旦跨质膜转运，这些GQD的带负电荷的官能团将以自清洁功能离开膜，并保持足够小的尺寸，以实现通过核膜进入核的渗透。我们的研究表明，IFP是肿瘤细胞核特异靶向的一种先前未被认识的机制，并表明磺酸GQDs可能会发展成为用于肿瘤特异性成像和治疗的新型工具。