Inhibitory effect of aptamer-carbon dot nanomaterial-siRNA complex on the metastasis of hepatocellular carcinoma cells by interfering with FMRP

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Abstract

<p class="first" id="d1046260e123">Using small interfering RNA (siRNA) for the specific gene-silencing has been a novel therapeutic method for the treatment of incurable diseases such as malignancies. However, it remains a challenge whether siRNA can be safely and effectively delivered into target cells. Therefore, we synthesized fluorescent carbon dots (CDs) as a gene vector at the siRNA delivery system that induced efficient gene knockdown in vitro while binding aptamer AS1411 to resolve the difficulty in cell targeting. We found that CDs with adequate biocompatibility can improve the efficiency of cellular uptake of siRNA. CLSM and FCM results showed that CDs were mainly localized in the cytoplasm and emitted bright green fluorescence. In addition, the CD/siRNA delivery system mediated by the aptamer AS1411 effectively silenced the expression of Fragile X mental retardation protein (FMRP) and successfully inhibited the migration and invasive propensity of hepatocellular carcinoma (HCC) cells. In summary, we have synthesized a valuable siRNA delivery vector enabling not only bioimaging but also effective downregulation of gene expression, which is indicative of an efficient potential for gene delivery and therapy. </p>

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Hepatocellular carcinoma

Alejandro Forner, María E Reig, Jordi Bruix (2018)

Hepatocellular carcinoma appears frequently in patients with cirrhosis. Surveillance by biannual ultrasound is recommended for such patients because it allows diagnosis at an early stage, when effective therapies are feasible. The best candidates for resection are patients with a solitary tumour and preserved liver function. Liver transplantation benefits patients who are not good candidates for surgical resection, and the best candidates are those within Milan criteria (solitary tumour ≤5 cm or up to three nodules ≤3 cm). Image-guided ablation is the most frequently used therapeutic strategy, but its efficacy is limited by the size of the tumour and its localisation. Chemoembolisation has survival benefit in asymptomatic patients with multifocal disease without vascular invasion or extrahepatic spread. Finally, sorafenib, lenvatinib, which is non-inferior to sorafenib, and regorafenib increase survival and are the standard treatments in advanced hepatocellular carcinoma. This Seminar summarises the scientific evidence that supports the current recommendations for clinical practice, and discusses the areas in which more research is needed.

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Hepatocellular Carcinoma

Dan L Longo, Augusto Villanueva (2019)

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Luminescent Carbon Nanodots: Emergent Nanolights

Sheila Baker, Gary A Baker (2010)

Similar to its popular older cousins the fullerene, the carbon nanotube, and graphene, the latest form of nanocarbon, the carbon nanodot, is inspiring intensive research efforts in its own right. These surface-passivated carbonaceous quantum dots, so-called C-dots, combine several favorable attributes of traditional semiconductor-based quantum dots (namely, size- and wavelength-dependent luminescence emission, resistance to photobleaching, ease of bioconjugation) without incurring the burden of intrinsic toxicity or elemental scarcity and without the need for stringent, intricate, tedious, costly, or inefficient preparation steps. C-dots can be produced inexpensively and on a large scale (frequently using a one-step pathway and potentially from biomass waste-derived sources) by many approaches, ranging from simple candle burning to in situ dehydration reactions to laser ablation methods. In this Review, we summarize recent advances in the synthesis and characterization of C-dots. We also speculate on their future and discuss potential developments for their use in energy conversion/storage, bioimaging, drug delivery, sensors, diagnostics, and composites.