Synthesis of graphene quantum dots and their applications in drug delivery
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Journal of Nanobiotechnology Open Access
REVIEW
Synthesis of graphene quantum dots and their applications in drug delivery Changhong Zhao1,2*, Xuebin Song1, Ya Liu2, Yifeng Fu2, Lilei Ye3, Nan Wang3, Fan Wang1, Lu Li1, Mohsen Mohammadniaei4, Ming Zhang4, Qiqing Zhang1* and Johan Liu2,5*
Abstract This review focuses on the recent advances in the synthesis of graphene quantum dots (GQDs) and their applications in drug delivery. To give a brief understanding about the preparation of GQDs, recent advances in methods of GQDs synthesis are first presented. Afterwards, various drug delivery-release modes of GQDs-based drug delivery systems such as EPR-pH delivery-release mode, ligand-pH delivery-release mode, EPR-Photothermal delivery-Release mode, and Core/Shell-photothermal/magnetic thermal delivery-release mode are reviewed. Finally, the current challenges and the prospective application of GQDs in drug delivery are discussed. Keywords: Graphene quantum dots, Top-down, Bottom-up, Drug delivery, Delivery-release mode Introduction GQDs are graphene blocks with two-dimensional (2D) transverse size (less than 100 nm) [1] and excellent chemical [2], physical [3], and biological properties [4, 5]. An ideal GQD consists of only one atomic layer of carbon atoms. However, most of the synthesized GQDs also contain functional groups like oxygen and hydrogen, and usually have multiple atomic layers with sizes less than 10 nm [6]. Due to its small size, GQD has a better prospect in biomedical applications than graphene or graphene oxide (GO) [7]. However, prior to designing GQDs into practical applications, their biocompatibility and toxicity are still the main concerns. Studies have shown that GQDs have good biocompatibility [8–10] and low biotoxicity [11, 12]. Xie et al. [13] studied the cytotoxicity and autophagy induction of three kinds of GQDs, including *Correspondence: [email protected]; [email protected]; johan. [email protected] 1 School of Life Sciences and Technology, Xinxiang Medical University, Xinxiang 453003, P. R. China 2 Electronics Materials and Systems Laboratory, Department of Microtechnology and Nanoscience, Chalmers University of Technology, 412 96 Gothenburg, Sweden Full list of author information is available at the end of the article
cGQDs (HOOC-GQDs), hGQDs (HO-GQDs), aGQDs (H2N-GQDs), using lung cancer A549 cells as models. The results showed that hGQDs were the most toxic, leading to significant cell death at 100 μg/mL of hGQD concentration, while cGQDs and aGQDs showed no cytotoxicity within the measured concentration range. Besides cGQDs, aGQDs, and hGQDs can induce autophagy to varying degrees, as shown in Table 1. Further analysis of autophagy pathway showed that all GQDs could significantly activate p-p38MAPK, while p-ERK1/2 was inhibited by aGQDs and hGQDs but activated by cGQDs. The aGQDs and cGQDs inhibited p-JNK and hGQDs activated p-JNK. On the other hand, Akt was activated by hGQDs, but inhibited by aGQDs. The inhibition of 3-MA on autophagy significantly increased the cytotoxicity of GQ
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