Lysosome–mitochondria-mediated Apoptosis Specifically Evoked in Cancer Cells Induced By Gold Nanorods

Zhang, Fulei; Gong, Jing; Sun, Yun; Chen, Di; Wang, Jie; Wang, Ying; Guo, Mengfang; Li, Wei

doi:10.2217/nnm-2016-0139

Cited by 28 publications

(19 citation statements)

References 48 publications

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“…For instance, Au-NPs induced apoptosis in MCF-7 and N87 cancer cell lines by disrupting lysosomes and mitochondria, but this effect did not appear in normal Chinese hamster ovary (CHO) and 293T cell lines. This observation further supports our conclusion that nanoparticle-mediated cell killing enhancement may be located in the cytoplasm, but more importantly gives a perspective of selective nanoparticle toxicity for tumor cells [64,69]. Interestingly, from the opposite point of view, some radio-protective chemicals (amifostine) protect normal cells from radiation effects but delay DSB repair in tumor cells [20].…”

Section: Discussionsupporting

confidence: 78%

Challenges and Contradictions of Metal Nano-Particle Applications for Radio-Sensitivity Enhancement in Cancer Therapy

Pagáčová

Štefančíková

Schmidt-Kaler

et al. 2019

IJMS

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From the very beginnings of radiotherapy, a crucial question persists with how to target the radiation effectiveness into the tumor while preserving surrounding tissues as undamaged as possible. One promising approach is to selectively pre-sensitize tumor cells by metallic nanoparticles. However, though the “physics” behind nanoparticle-mediated radio-interaction has been well elaborated, practical applications in medicine remain challenging and often disappointing because of limited knowledge on biological mechanisms leading to cell damage enhancement and eventually cell death. In the present study, we analyzed the influence of different nanoparticle materials (platinum (Pt), and gold (Au)), cancer cell types (HeLa, U87, and SKBr3), and doses (up to 4 Gy) of low-Linear Energy Transfer (LET) ionizing radiation (γ- and X-rays) on the extent, complexity and reparability of radiation-induced γH2AX + 53BP1 foci, the markers of double stand breaks (DSBs). Firstly, we sensitively compared the focus presence in nuclei during a long period of time post-irradiation (24 h) in spatially (three-dimensionally, 3D) fixed cells incubated and non-incubated with Pt nanoparticles by means of high-resolution immunofluorescence confocal microscopy. The data were compared with our preliminary results obtained for Au nanoparticles and recently published results for gadolinium (Gd) nanoparticles of approximately the same size (2–3 nm). Next, we introduced a novel super-resolution approach—single molecule localization microscopy (SMLM)—to study the internal structure of the repair foci. In these experiments, 10 nm Au nanoparticles were used that could be also visualized by SMLM. Altogether, the data show that different nanoparticles may or may not enhance radiation damage to DNA, so multi-parameter effects have to be considered to better interpret the radiosensitization. Based on these findings, we discussed on conclusions and contradictions related to the effectiveness and presumptive mechanisms of the cell radiosensitization by nanoparticles. We also demonstrate that SMLM offers new perspectives to study internal structures of repair foci with the goal to better evaluate potential differences in DNA damage patterns.

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Section: Discussionsupporting

confidence: 78%

Challenges and Contradictions of Metal Nano-Particle Applications for Radio-Sensitivity Enhancement in Cancer Therapy

Pagáčová

Štefančíková

Schmidt-Kaler

et al. 2019

IJMS

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“…GNPs (10–40 nm) induced apoptosis in Vero cells, but not in MRC-5 or NIH3T3 cells [ 72 ]. Also, it was observed that GNRs (50–60 nm × 20–30 nm) induced apoptosis in cancer cell lines MCF-7 and N87 by affecting lysosomes and mitochondria, while it showed a negligible impact on normal Chinese hamster ovary (CHO) and 293T cell lines, indicating GNR’s potential use in cancer treatment [ 73 ].…”

Section: Gnp-induced Apoptosismentioning

confidence: 99%

Gold Nanoparticle-Induced Cell Death and Potential Applications in Nanomedicine

Sun

Jia

Jiang

et al. 2018

IJMS

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Cell death is crucial to human health and is related to various serious diseases. Therefore, generation of new cell death regulators is urgently needed for disease treatment. Nanoparticles (NPs) are now routinely used in a variety of fields, including consumer products and medicine. Exhibiting stability and ease of decoration, gold nanoparticles (GNPs) could be used in diagnosis and disease treatment. Upon entering the human body, GNPs contact human cells in the blood, targeting organs and the immune system. This property results in the disturbance of cell function and even cell death. Therefore, GNPs may act as powerful cell death regulators. However, at present, we are far from establishing a structure–activity relationship between the physicochemical properties of GNPs and cell death, and predicting GNP-induced cell death. In this review, GNPs’ size, shape, and surface properties are observed to play key roles in regulating various cell death modalities and related signaling pathways. These results could guide the design of GNPs for nanomedicine.

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“…After the cells reached 80% confluence, they were treated with drug at 37 °C with 5% CO 2 for 48 h. The cells were trypsinized, collected, washed, and finally suspended in one-time binding buffer, followed by staining with an Annexin-V antibody labeled with Alexa Fluor-488 for 15 min at RT in the dark. Then, the apoptotic cells were analyzed by flow cytometry [ 24 ]. For each sample, at least 1 × 10 4 cells were analyzed.…”

Section: Methodsmentioning

confidence: 99%

A Micelle Self-Assembled from Doxorubicin-Arabinoxylan Conjugates with pH-Cleavable Bond for Synergistic Antitumor Therapy

Wang

Dong

et al. 2017

Nanoscale Res Lett

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Nanomedicine offers new hope to overcome the low solubility and high side toxicity to normal tissue appeared in traditional chemotherapy. The biocompatibility and intracellular drug accumulation is still a big challenge for the nano-based formulations. Herein, a medical-used biocompatible arabinoxylan (AX) is used to develop to delivery chemodrug doxorubicin (DOX). The solubility of DOX is obviously enhanced via the hydrogen bond formed with AX which results in an amphiphilic AX-DOX. A micelle with pH-cleavable bond is thus self-assembled from such AX-DOX with DOX core and AX shell. The inner DOX can be easily released out at low intracellular pH, which obviously enhanced its in vitro cytotoxicity against breast cancer cells (MCF-7). Interestingly, an unexpected apoptosis is evoked except for the proliferation inhibition. Moreover, the therapeutic effects are further synergistically promoted by the enhanced permeability and retention (EPR) and intracellular pH-triggered drug release. Consequently, the in vivo intratumor accumulation of DOX, the tumor inhibition was significantly promoted after intravenous administration to the Balb/c nude mice bearing MCF-7 tumors. These in vitro/vivo results indicated that the AX-DOX micellular formulation holds high potential in cancer therapy.Graphical Abstract

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Lysosome–mitochondria-mediated Apoptosis Specifically Evoked in Cancer Cells Induced By Gold Nanorods

Abstract: These findings indicated that GNR-induced apoptosis specifically in cancer cells by affecting lysosomes and mitochondria.

Cited by 28 publications

References 48 publications

Challenges and Contradictions of Metal Nano-Particle Applications for Radio-Sensitivity Enhancement in Cancer Therapy

Challenges and Contradictions of Metal Nano-Particle Applications for Radio-Sensitivity Enhancement in Cancer Therapy

Gold Nanoparticle-Induced Cell Death and Potential Applications in Nanomedicine

A Micelle Self-Assembled from Doxorubicin-Arabinoxylan Conjugates with pH-Cleavable Bond for Synergistic Antitumor Therapy

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