Targeted imaging and induction of apoptosis of drug-resistant hepatoma cells by miR-122-loaded graphene-InP nanocompounds

Abstract

BackgroundCurrently, graphene oxide has attracted growing attention as a drug delivery system due to its unique characteristics. Furthermore, utilization of microRNAs as biomarkers and therapeutic strategies would be particularly attractive because of their biological mechanisms and relatively low toxicity. Therefore, we have developed functionalized nanocompounds consisted of graphene oxide, quantum dots and microRNA, which induced cancer cells apoptosis along with targeted imaging.ResultsIn the present study, we synthesized a kind of graphene-P-gp loaded with miR-122-InP@ZnS quantum dots nanocomposites (GPMQNs) that, in the presence of glutathione, provides controlled release of miR-122. The miR-122 actively targeted liver tumor cells and induced their apoptosis, including drug-resistant liver tumor cells. We also explored the near-infrared fluorescence and potential utility for targeting imaging of InP@ZnS quantum dots. To further understand the molecular mechanism of GPMQNs-induced apoptosis of drug-resistant HepG2/ADM hepatoma cells, the relevant apoptosis proteins and signal pathways were explored in vitro and in vivo. Furthermore, near-infrared GPMQNs, which exhibited reduced photon scattering and auto-fluorescence, were applied for tumor imaging in vivo to allow for deep tissue penetration and three-dimensional imaging.ConclusionIn conclusion, techniques using GPMQNs could provide a novel targeted treatment for liver cancer, which possessed properties of targeted imaging, low toxicity, and controlled release.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-016-0237-2) contains supplementary material, which is available to authorized users.

RETRACTED ARTICLE: Circular RNA ABCB10 promotes hepatocellular carcinoma progression by increasing HMG20A expression by sponging miR-670-3p

“…For example, mi R-122 is significantly down-regulated in liver cancer, especially in liver metastasis. The overexpression of mi R-122 can not only significantly reduce the migration and invasion ability of liver cancer cells, but also inhibited liver cancer metastasis through the inhibition of angiogenesis [34]. It was screened miR-670-3p as a target gene for circABCB10 by database.…”

Knockdown of SOX2OT inhibits the malignant biological behaviors of glioblastoma stem cells via up-regulating the expression of miR-194-5p and miR-122

“…MiR-122 is decreased in HBV-related hepatocellular carcinoma, and its expression is negatively correlated with tumor size, lymph node metastasis, TNM stage, histological type, and cell differentiation [ 53 ]. A kind of graphene-P-gp loaded with miR-122-InP@ZnS quantum dots nanocomposites induced drug-resistant liver tumor cells apoptosis [ 54 ]. Combined with the effect of miR-122 on GSCs in this study, we suggest that miR-122 may act as a tumor suppressor in gastric cancer, liver cancer and glioma.…”

The Underlying Mechanisms of Noncoding RNAs in the Chemoresistance of Hepatocellular Carcinoma

“…118 In addition, the delivery of miR-122 by multifunctional graphene-P-gp loaded with miR-122-InP@ZnS quantum dots (QDs) nanocomposites (GPMQNs) selectively targeted HCC xenograft tumors and alleviated DOX resistance by inducing apoptosis in HCC. 119 These studies regarding experimental miR-122-based therapies are encouraging, but their therapeutic efficacy warrants further evaluation in clinical trials. Similarly, miR-101 has been affirmed to be a critical tumor-suppressive miRNA in HCC.…”