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Protein Kinase C-delta Inhibitor Peptide Formulation using Gold Nanoparticles
Published on: March 9, 2019
Cyclic Peptide Modified Gold Clusters Induce Lung Tumor Cell Apoptosis via Generating Intracellular Oxidative Stress
Zhesheng He1, Zhongying Du2, Chunyu Zhang2
1CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.
Abstract:
Metastatic lung cancer is the leading cause of death for cancer patients. Although many chemical drugs were developed for cancer treatment, metastatic cancer mortality did not decrease significantly. In this article, we designed an Au clusters (AuCs) modified by cyclic RGD peptides which well target the integrin of human lung carcinoma cells (A549). The RGD-AuCs could well induce A549 cells apoptosis, but have no cytotoxicity on the human bronchial epithelial cells (16HBE), which are normal cells support respiratory system. The AuCs could be internalized and localized in the lysosomes of A549 tumor cells and further release into cytoplasma. We found the ROS level was increased by AuCs, and such high ROS level finally leads to depolarization of mitochondria. Eventually, the AuCs stimulating mitochondria related apoptosis pathway to induce A549 tumor cells apoptosis. We deduce the gold clusters would be an effective therapeutic candidate to against metastatic lung tumor in the future studies.
Insights
New gold clusters (AuCs) target lung cancer cells, inducing apoptosis without harming normal cells. This discovery offers a promising therapeutic candidate for metastatic lung tumors.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Metastatic lung cancer remains a leading cause of cancer-related mortality.
- Current chemotherapies have limited efficacy in reducing metastatic cancer deaths.
- Targeted therapies are needed to selectively eliminate cancer cells.
Purpose of the Study:
- To design and evaluate cyclic RGD peptide-modified gold clusters (RGD-AuCs) for targeted lung cancer therapy.
- To assess the efficacy and specificity of RGD-AuCs against human lung carcinoma cells (A549).
- To investigate the mechanism of RGD-AuCs-induced apoptosis in A549 cells.
Main Methods:
- Synthesis of RGD-AuCs targeting integrins on A549 cells.
- In vitro cytotoxicity assays on A549 and normal human bronchial epithelial cells (16HBE).
- Cellular uptake and intracellular localization studies using microscopy.
- Analysis of reactive oxygen species (ROS) levels and mitochondrial membrane potential.
- Investigation of mitochondria-mediated apoptosis pathways.
Main Results:
- RGD-AuCs selectively induced apoptosis in A549 cells.
- No significant cytotoxicity was observed in normal 16HBE cells.
- AuCs were internalized by A549 cells and localized in lysosomes, then released into the cytoplasm.
- AuCs significantly increased intracellular ROS levels, leading to mitochondrial depolarization.
- AuCs activated mitochondria-related apoptosis pathways, causing A549 cell death.
Conclusions:
- RGD-AuCs demonstrate targeted therapeutic potential against metastatic lung cancer.
- The mechanism involves ROS generation, mitochondrial dysfunction, and apoptosis induction.
- Gold clusters represent a promising future therapeutic candidate for lung tumors.
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