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Exosomal miRNA Analysis in Non-small Cell Lung Cancer NSCLC Patients' Plasma Through qPCR: A Feasible Liquid Biopsy Tool
Published on: May 27, 2016
Extracellular vesicle-like particles from Taraxacum mongolicum suppress non-small cell lung cancer associated with
Wei Peng1, Renyi Yang1, Jincheng Tang2
1Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine, Hunan Academy of Chinese Medicine, Changsha, Hunan, China.
Introduction:
Plant-derived extracellular vesicle-like particles (EVLPs) are emerging as natural, orally deliverable nanomaterials, but their antitumor activity and mitochondrial mechanisms in non-small cell lung cancer (NSCLC) remain insufficiently defined.
Methods:
Taraxacum mongolicum-derived EVLPs (TM-EVLPs) were isolated by enzymatic digestion and differential ultracentrifugation and characterized by nanoparticle tracking analysis, transmission electron microscopy, and protein profiling. Cellular uptake and antitumor effects were evaluated in A549 and H1975 cells using proliferation, migration, invasion, epithelial-mesenchymal transition, and mitochondrial function assays. In vivo efficacy and safety were assessed in an A549 xenograft model after oral TM-EVLP administration.
Results:
DiI-labeled TM-EVLPs showed clear cell-associated signals after incubation and washing. TM-EVLPs inhibited NSCLC cell viability, DNA synthesis, clonogenicity, migration, and invasion, with more consistent effects at higher concentrations, and increased E-cadherin but decreased N-cadherin expression. TM-EVLP treatment was associated with mitochondrial membrane potential depolarization, increased mitochondrial reactive oxygen species, reduced ATP production, disrupted cristae ultrastructure, and decreased oxidative phosphorylation complex subunits. In xenograft-bearing mice, oral TM-EVLPs (5-20 mg/kg, 15 days) reduced tumor growth, decreased Ki-67 and PCNA staining, increased TUNEL positivity, recapitulated mitochondrial impairment in tumors, and caused no overt histological injury in major organs.
Discussion:
TM-EVLPs suppress NSCLC malignant phenotypes in association with constrained mitochondrial bioenergetics and increased oxidative stress, supporting a mitochondria-centered stress-linked working model.
Insights
Plant-derived nanoparticles show promise against non-small cell lung cancer (NSCLC). Taraxacum mongolicum-derived EVLPs (TM-EVLPs) target cancer cell mitochondria, reducing tumor growth and improving safety for oral delivery.
Area of Science:
- Biotechnology
- Nanomedicine
- Oncology
Background:
- Plant-derived extracellular vesicle-like particles (EVLPs) are emerging as orally deliverable nanomaterials.
- The antitumor activity and mitochondrial mechanisms of EVLPs in non-small cell lung cancer (NSCLC) require further investigation.
Purpose of the Study:
- To investigate the antitumor activity of Taraxacum mongolicum-derived EVLPs (TM-EVLPs) in NSCLC.
- To elucidate the mitochondrial mechanisms underlying TM-EVLP-mediated antitumor effects.
- To evaluate the in vivo efficacy and safety of orally administered TM-EVLPs.
Main Methods:
- TM-EVLPs were isolated and characterized using nanoparticle tracking analysis, transmission electron microscopy, and protein profiling.
- Cellular uptake and antitumor effects were assessed in NSCLC cell lines (A549, H1975) via proliferation, migration, invasion, EMT, and mitochondrial function assays.
- In vivo efficacy and safety were evaluated in an A549 xenograft mouse model following oral TM-EVLP administration.
Main Results:
- TM-EVLPs demonstrated cellular uptake and inhibited NSCLC cell viability, DNA synthesis, clonogenicity, migration, and invasion.
- TM-EVLP treatment led to mitochondrial membrane depolarization, increased reactive oxygen species, reduced ATP production, and impaired oxidative phosphorylation.
- Oral TM-EVLPs reduced tumor growth in vivo, decreased proliferation markers, increased apoptosis, and induced mitochondrial impairment in tumors without significant organ toxicity.
Conclusions:
- TM-EVLPs suppress NSCLC malignant phenotypes by impairing mitochondrial bioenergetics and increasing oxidative stress.
- These findings support a mitochondria-centered, stress-linked mechanism for TM-EVLP antitumor activity.
- TM-EVLPs represent a promising, orally deliverable nanotherapeutic for NSCLC treatment.
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