Doped Graphene Quantum Dots for Intracellular Multicolor Imaging and Cancer Detection
Doped Graphene Quantum Dots for Intracellular Multicolor Imaging and Cancer Detection
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DOI：
10.1021/acsbiomaterials.9b00603
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发表时间：
2019-09-01
影响因子：
5.8
通讯作者：
Naumov, Anton V.
中科院分区：
文献类型：
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作者：
Campbell, Elizabeth;Hasan, Md. Tanvir;Naumov, Anton V.
尽管纳米医学取得了显着进展，但生物相容性、积累衍生的毒性以及缺乏传感和体内成像能力等问题阻碍了大多数纳米载体向临床的转化。为了解决这个问题，我们利用氮，硼/氮和硫掺杂的石墨烯量子点（GQD）作为完全生物相容的多功能平台，允许可见光/近红外成像和癌症传感。这些GQD是由单一生物相容性葡糖胺前体在一步合成中可缩放地产生的，是水溶性的，在1 mg/mL的高浓度下没有显示出细胞毒性，并且在生物环境中在36 h时表现出实质性降解，如通过TEM成像所验证的。由于它们的小尺寸，GQD表现出有效的内化在12小时最大化，随后进一步降解/排泄。它们在蓝色/绿色和近红外的高产量内在荧光允许其自身或与其他荧光团组合进行体外成像，并提供体内近红外荧光跟踪的能力。此外，氮和硫掺杂的GQD表现出pH依赖性荧光响应，其被成功地用作癌细胞的酸性细胞外环境的传感机制。它允许确定性的，比率光谱之间的区别癌（HeLa和MCF-7细胞）与健康（HEK-293细胞）的环境与基本强度比为1.6至8。这些结果表明，在这项工作中开发的完全生物相容的GQD作为多功能候选物，用于体外递送活性剂，可见光/近红外荧光成像和癌性环境的pH传感。
Despite significant advances of nanomedicine, the issues of biocompatibility, accumulation-derived toxicity, and the lack of sensing and in vivo imaging capabilities hamper the translation of most nanocarriers into clinic. To address this, we utilize nitrogen, boron/nitrogen, and sulfur-doped graphene quantum dots (GQDs) as fully biocompatible multifunctional platforms allowing for multicolor visible/near-IR imaging and cancer-sensing. These GQDs are scalably produced in one-step synthesis from a single biocompatible glucosamine precursor, are water-soluble, show no cytotoxicity at high concentrations of 1 mg/mL, and demonstrate substantial degradation at 36 h in biological environments as verified by TEM imaging. Because of their small sizes, GQDs exhibit efficient internalization maximized at 12 h followed by further degradation/excretion. Their high-yield intrinsic fluorescence in blue/green and near-infrared allows for multicolor in vitro imaging on its own or in combination with other fluorophores, and offers the capabilities for in vivo near-IR fluorescence tracking. Additionally, nitrogen- and sulfur-doped GQDs exhibit pH-dependent fluorescence response that is successfully utilized as a sensing mechanism for acidic extracellular environments of cancer cells. It allows for the deterministic, ratiometric spectral discrimination between cancerous (HeLa and MCF-7 cell) versus healthy (HEK-293 cell) environments with substantial intensity ratios of 1.6 to 8. These results suggest fully biocompatible GQDs developed in this work as multifunctional candidates for in vitro delivery of active agents, multicolor visible/near-IR fluorescence imaging, and pH-sensing of cancerous environments.