Mitochondrial delivery of microRNA mimic let-7b to NSCLC cells by PAMAM-based nanoparticles
Autor: | Parisa Norouzi, Farid Abedin Dorkoosh, Mohammad Hossein Ghahremani, Masoud Soleimani, Hamid Akbari, Mohsen Amini, Hamed Samadi, Alireza Naderi Sohi, Reza Baradaran Eftekhari, Niloufar Maghsoudnia |
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Rok vydání: | 2020 |
Předmět: |
Programmed cell death
Dendrimers Lung Neoplasms Cell Survival Cell Respiratory chain Pharmaceutical Science Gene Expression Apoptosis 02 engineering and technology Gene delivery Mitochondrion 03 medical and health sciences 0302 clinical medicine Carcinoma Non-Small-Cell Lung Cell Line Tumor medicine Humans Cell Proliferation A549 cell biology Chemistry CD44 021001 nanoscience & nanotechnology Cell biology Mitochondria MicroRNAs medicine.anatomical_structure A549 Cells 030220 oncology & carcinogenesis Cancer cell biology.protein Nanoparticles 0210 nano-technology |
Zdroj: | Journal of drug targeting. 28(7-8) |
ISSN: | 1029-2330 |
Popis: | Many biological mechanisms including cellular metabolism and cell death are regulated by mitochondria known as powerhouse of the cell. Recently, let-7b, a tumour-suppressor microRNA has been detected in mitochondria of human cells targeting several mitochondrial-encoded respiratory chain genes. Triphenylphosphonium cation (TPP) is one of the major classes of mitochondriotropics that possess the ability of specifically targeting the mitochondria. PAMAM dendrimers are one of the most available agents in gene delivery due to their well-defined and beneficial features such as large density of surface functional groups. Hyaluronic acid (HA), a natural polysaccharide has been demonstrated to have the abilities such as good biocompatibility and targeting CD44 overexpressed receptors on non-small cell lung cancer (NSCLC) cells. In this research, let-7b-PAMAM (G5)-TPP and let-7b-PAMAM (G5)-TPP-HA nano-carriers were designed to deliver let-7b miRNA mimic to NSCLC cells' mitochondria as a novel way of cancer cells inhibition. Nano-carriers were capable of being successfully taken up by A549 cells and localised in mitochondria environment. Let-7b loaded nanoparticles reduced cell viability and induced apoptosis significantly. Expression of genes involved in mitochondrial oxidative function was decreased resulting in nanoparticles effect on mitochondria. Application of mitochondria targeted-miRNA delivery systems could regulate cellular functions to inhibit lung cancer. |
Databáze: | OpenAIRE |
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