Cancer Therapeutic siRNA Delivery and Imaging by Nitrogen- and Neodymium-Doped Graphene Quantum Dots.
Cancer Therapeutic siRNA Delivery and Imaging by Nitrogen- and Neodymium-Doped Graphene Quantum Dots.
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DOI：
10.1021/acsbiomaterials.3c00369
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发表时间：
2023-05
影响因子：
5.8
通讯作者：
Alina Valimukhametova;B. Lee;U. C. Topkiran;Klara Gries;R. Gonzalez-Rodriguez;J. Coffer;G. Akkaraju;A. Naumov
中科院分区：
文献类型：
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作者：
Alina Valimukhametova;B. Lee;U. C. Topkiran;Klara Gries;R. Gonzalez-Rodriguez;J. Coffer;G. Akkaraju;A. Naumov
虽然小干扰RNA（siRNA）技术已成为实现癌症特异性基因治疗的强大工具，但由于单独的基因无法进行细胞转染、血液中的siRNA稳定性差以及缺乏递送能力，其向临床的转化仍然受到阻碍。跟踪能力。最近，石墨烯量子点（GQD）已成为一种新的平台，允许在可见光和近红外区域的靶向药物输送和荧光图像跟踪。这些能力可以帮助克服siRNA治疗的主要障碍。在这里，我们第一次利用生物相容的氮和钕掺杂的石墨烯量子点（分别为NGQD和Nd-NGQD）来递送Kirsten大鼠肉瘤病毒（KRAS）和表皮生长因子受体（EGFR）siRNA，有效对抗各种癌症类型。负载有siRNA的GQD非共价地促进siRNA成功转染到HeLa细胞中，在生物相容性GQD浓度为375 μg/mL时通过共聚焦荧光显微镜证实。虽然GQD平台提供可见荧光跟踪，但Nd掺杂能够实现更深的组织近红外荧光成像，适用于体外和体内应用。GQD/siRNA复合物的治疗功效通过在HeLa细胞中在纳摩尔siEGFR和siKRAS浓度下成功的蛋白质敲低来验证。测试了一系列GQD/siRNA负载比和有效载荷，以最终提供低至31- 45%的蛋白质表达的实质性抑制，与常规Lipofectamine介导的递送相当。这证明了GQD用于siRNA和基因的无毒递送的有前途的潜力，并辅之以多波长图像跟踪。
While small interfering RNA (siRNA) technology has become a powerful tool that can enable cancer-specific gene therapy, its translation to the clinic is still hampered by the inability of the genes alone to cell transfection, poor siRNA stability in blood, and the lack of delivery tracking capabilities. Recently, graphene quantum dots (GQDs) have emerged as a novel platform allowing targeted drug delivery and fluorescence image tracking in visible and near-infrared regions. These capabilities can aid in overcoming primary obstacles to siRNA therapeutics. Here, for the first time, we utilize biocompatible nitrogen- and neodymium-doped graphene quantum dots (NGQDs and Nd-NGQDs, respectively) for the delivery of Kirsten rat sarcoma virus (KRAS) and epidermal growth factor receptor (EGFR) siRNA effective against a variety of cancer types. GQDs loaded with siRNA noncovalently facilitate successful siRNA transfection into HeLa cells, confirmed by confocal fluorescence microscopy at biocompatible GQD concentrations of 375 μg/mL. While the GQD platform provides visible fluorescence tracking, Nd doping enables deeper-tissue near-infrared fluorescence imaging suitable for both in vitro and in vivo applications. The therapeutic efficacy of the GQD/siRNA complex is verified by successful protein knockdown in HeLa cells at nanomolar siEGFR and siKRAS concentrations. A range of GQD/siRNA loading ratios and payloads are tested to ultimately provide substantial inhibition of protein expression down to 31-45%, comparable with conventional Lipofectamine-mediated delivery. This demonstrates the promising potential of GQDs for the nontoxic delivery of siRNA and genes in general, complemented by multiwavelength image tracking.