Simultaneous detection of multiple targets involved in the PI3K/AKT pathway for investigating cellular migration and invasion with a multicolor fluorescent nanoprobe

Luan, Mingming; Li, Na; Pan, Wei; Yang, Limin; Yu, Zhengze; Tang, Bo

doi:10.1039/c6cc07605j

Cited by 52 publications

(40 citation statements)

References 28 publications

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“…[9][10][11][12] For example, the Tang group developed multicolor uorescent nanoprobes based on gold nanoparticles (GNPs) for evaluating cellular migration and invasion by simultaneously imaging miRNA-221, PTEN mRNA and MMP9 in living cells. 13 The Zhu group assembled multicomponent nucleic acid enzymes onto the surface of mesoporous silica-coated gold nanorods as multifunctional nanodevices for intracellular miRNA-21 and miRNA-145 in situ imaging. 14 However, the preparation processes of these nanoprobes are oen complicated and timeconsuming, and their stability, biocompatibility and cell permeation ability are also not satisfactory for in vivo diagnosis, which has driven researchers to nd other substitutes.…”

Section: Introductionmentioning

confidence: 99%

Accurate cancer cell identification and microRNA silencing induced therapy using tailored DNA tetrahedron nanostructures

Xia

et al. 2020

Chem. Sci.

100

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Section: Introductionmentioning

confidence: 99%

Accurate cancer cell identification and microRNA silencing induced therapy using tailored DNA tetrahedron nanostructures

Xia

et al. 2020

Chem. Sci.

100

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“…It is necessary to develop a quicker, simpler and more accurate approach to sense multiplexed microRNAs in live cells. 30 …”

Section: Introductionmentioning

confidence: 99%

“…This two-color-based nanoflares could provide an easy, noninvasive, instantaneous and intuitive way to imaging multiplex miRNAs in living cells. 30 …”

Section: Introductionmentioning

confidence: 99%

Two-Color-Based Nanoflares for Multiplexed MicroRNAs Imaging in Live Cells

Li¹,

Huang²,

Yang³

et al. 2018

Nanotheranostics

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MicroRNAs (miRNAs) have become an ideal biomarker candidate for early diagnosis of diseases. But various diseases involve changes in the expression of different miRNAs. Therefore, multiplexed assay of miRNAs in live cells can provide critical information for our better understanding of their roles in cells and further validating of their function in clinical diagnoses. Simultaneous detection of multiple biomarkers could effectively improve the accuracy of early cancer diagnosis. Here, we develop the two-color-based nanoflares for simultaneously detecting two distinct miRNA targets inside live cells. The nanoflares consist of gold nanoparticles (AuNPs) functionalized with a dense shell of recognition sequences hybridized to two short fluorophore-labeled DNA molecules, termed “flares”. In this conformation, the close proximity of the fluorophore to the AuNPs surface leads to quenching of the fluorescence. However, when target miRNAs bind to the recognition sequence, the concomitant displacement of the flare can be detected as a corresponding increase in fluorescence. The results demonstrate that the two-color-based nanoflares can simultaneously detect miR-21 and miR-141 expression levels in various live cancer cells successfully. Compared to the traditional single-color-based nanoflares, the two-color-based nanoflares could offer more reliable and practical information for cancer detection, improving the accuracy of early disease diagnosis.

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“…The combined effects of TiO 2 (Gd)-TPP NPs and X-ray (4 Gy) irradiation on the migration and invasion capabilities of MCF-7 cells were also studied using wound-healing assays and cell invasion assays 39. The scratched region in the group of TiO 2 (Gd)-TPP+X-ray was wider than that in the cells treated with TiO 2 (Gd)+X-ray or with X-ray at 36 h after the creation of the scratch ( Figure S20A-B ), which suggested that the migration ability was significantly influenced by the nanosensitizer under X-ray irradiation.…”

Section: Resultsmentioning

confidence: 99%

Enhancement of mitochondrial ROS accumulation and radiotherapeutic efficacy using a Gd-doped titania nanosensitizer

Chen¹,

Li²,

Wang³

et al. 2019

Theranostics

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Radiotherapy is an extensively used treatment modality in the clinic and can kill malignant cells by generating cytotoxic reactive oxygen species (ROS). Unfortunately, excessive dosages of radiation are typically required because only a small proportion of the radiative energy is adsorbed by the soft tissues of a tumor, which results in the nonselective killing of normal cells and severe systemic side effects. An efficient nanosensitizer that makes cancer cells more sensitive to radiotherapy under a relatively low radiation dose would be highly desirable.Methods: In this study, we developed a Gd-doped titania nanosensitizer that targets mitochondria to achieve efficient radiotherapy. Upon X-ray irradiation, the nanosensitizer triggers a “domino effect” of ROS accumulation in mitochondria. This overabundance of ROS leads to mitochondrial permeability transition and ultimately irreversible cell apoptosis. Confocal laser imaging, western blotting and flow cytometry analysis were used to explore the biological process of intrinsic apoptosis induced by the nanosensitizer. Clonogenic survival assay, cell migration and invasion experiments were employed to evaluate the radiosensitizing effect of the nanosensitizer in vitro. Finally, to evaluate the therapeutic outcome of the nanosensitizer in vivo, MCF-7 tumor model was used.Results: Confocal laser images and western blotting data demonstrated that the nanosensitizer in conjunction with X-ray irradiation could induce cell apoptosis in ROS-mediated apoptotic signal pathways. A clonogenic survival assay revealed that cells treated with the prepared nanosensitizer exhibited a lower number of viable cell colonies than that of the nontargeted group under X-ray irradiation. Notably, with only a single dose of radiotherapy, the mitochondria-targeted nanosensitizer elicited the complete ablation of tumors in a mouse model.Conclusion: The designed nanosensitizer in combination with X-ray radiation exposure could be used for radiotherapy against cancer in living cells and in vivo. Moreover, the nanosensitizer with mitochondria targeting played a pivotal role in triggering a “domino effect” of ROS and cell apoptosis. The current strategy could provide new opportunities in designing efficient radiosensitizers for future cancer therapy.

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Simultaneous detection of multiple targets involved in the PI3K/AKT pathway for investigating cellular migration and invasion with a multicolor fluorescent nanoprobe

Abstract: We develop a multicolor fluorescent nanoprobe for assessing cellular migration and invasion by simultaneously imaging miRNA-221, PTEN mRNA and MMP-9 involved in the PI3K/AKT pathway which can regulate cellular mobility and invasiveness.

Cited by 52 publications

References 28 publications

Accurate cancer cell identification and microRNA silencing induced therapy using tailored DNA tetrahedron nanostructures

Accurate cancer cell identification and microRNA silencing induced therapy using tailored DNA tetrahedron nanostructures

Two-Color-Based Nanoflares for Multiplexed MicroRNAs Imaging in Live Cells

Enhancement of mitochondrial ROS accumulation and radiotherapeutic efficacy using a Gd-doped titania nanosensitizer

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