Harnessing Focal Adhesions to Accelerate p53 Accumulation and Anoikis of A549 Cells Using Colloidal Self-Assembled Patterns (cSAPs)

Objectives: Paclitaxel (Ptx) has been regarded as one of the most effective chemotherapeutic drugs for lung cancers. Increasing studies focused on the nano-delivery system of Ptx due to its poor solubility and hypersensitivity. The aim of the recent study was to investigate the antitumor effects of self-assembled Ptx nano-filaments for lung cancer cells. </P><P> Methods: In the present study, we designed and synthesized novel Ptx-loaded nano-filaments through conjugation of Ptx and succinic acid (SA) (Ptx-SA, P-NFs). Non-small cell lung cancer (NSCLC) A549 and H460 cells were used for detecting the antitumor effects of P-NFs, including cytotoxicity, apoptosis, and migration. Western blotting was performed for analyzing mechanism. Results: P-NFs nano-filaments exerted superior antitumor effects against NSCLC cells compared with free Ptx using cytotoxicity tests. Furthermore, P-NFs nano-filaments were much more effective in inducing NSCLC cells apoptosis and inhibiting A549 cells migration than free Ptx. To elucidate the underlying mechanisms, the expression of apoptotic and endoplasmic reticulum (ER) stress proteins was detected. The results indicated that P-NFs nano-filaments enhanced the expression of bax/bcl-2, protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1α (IRE1α), phospho- c-Jun N-terminal kinase (p-JNK), and C/EPB homologous protein (CHOP), which suggested that the strong antitumor effect of P-NFs nano-filaments may be partially attributed to the activation ER stress. The current work demonstrated that P-NFs nano-filaments showed superior cytotoxicity of lung cancer cells, highlighting a novel profile of nano-filaments delivery systems as potential strategies for facilitating the therapeutic efficacy of Ptx in lung cancer treatment.

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Effects of Biomimetic Shear Stress by Self-Assembled Gelatin Oleic Nanoparticles Containing Paclitaxel on the Behavior of Cancer Cell Lines in a Microfluidic System

10.20944/preprints201704.0023.v1 ◽

2017 ◽

Author(s):

Taehee Kang ◽

Thuy Thi Thanh Tran ◽

Kyung Taek Oh ◽

Han-Gon Choi ◽

Beom-Jin Lee

Keyword(s):

Shear Stress ◽

Cell Lines ◽

Cellular Uptake ◽

A549 Cells ◽

Drug Efficacy ◽

Microfluidic System ◽

Cellular Interactions ◽

Cellular Behaviors ◽

Self Assembled ◽

Static Conditions

Fluid flow in human body is generally known to influence a variety of cellular behaviors. Different nanoparticle properties as well as cell type, interaction with other cells and cellular environments also show significant effect on nanoparticle uptake and drug efficacy. The aim of this study was to evaluate the effect of shear stress on cellular behaviors of biocompatible and biodegradable nanoparticles to cancer cells (A549 cell lines) in a biomimetic microfluidic system. We prepared a gelatin-oleic conjugate (GOC) as an amphiphilic biomaterial to prepare self-assembled gelatin-oleic nanoparticles (GON). Coumarin-6 and paclitaxel were used as the fluorescence marker and model drug, respectively, and were loaded into GONs by incubation (C-GONs; PTX-GONs). Additionally, we evaluated the cellular uptake of fluorescence labeled C-GONs and the drug efficacy of PTX-GONs. The cellular uptake of C-GONs by A549 cells in the absence of shear stress revealed that the mean fluorescence intensity was slightly decreased compared to that in the presence of shear stress. The results also indicated that negatively charged PTX-GONs had a lower cancer killing effect under dynamic conditions than that under static conditions. It also suggested that fluidic shear stress did not significantly affect drug uptake and efficiency in case of PTX-GONs. The cellular interactions between nanoparticles and cells in drug delivery should be carefully examined according to the physicochemical properties of nanoparticles such as the type of materials, size and mainly surface charge in a biomimetic microfluidic condition.

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Disruption of Cell Adhesion and Cytoskeletal Networks by Thiol-Functionalized Silica-Coated Iron Oxide Nanoparticles

International Journal of Molecular Sciences ◽

10.3390/ijms21249350 ◽

2020 ◽

Vol 21 (24) ◽

pp. 9350

Author(s):

Karel Královec ◽

Lucie Melounková ◽

Marcela Slováková ◽

Nikola Mannová ◽

Miloš Sedlák ◽

...

Keyword(s):

Cell Adhesion ◽

Iron Oxide ◽

Biomedical Applications ◽

A549 Cells ◽

Focal Adhesions ◽

Lung Epithelial Cells ◽

Cell Cycle Distribution ◽

Functionalized Silica ◽

Extracellular Signal ◽

Cytoskeletal Networks

One of the major obstacles that limits the use of magnetic nanoparticles in biomedical applications is their potential toxicity. In the present study, we evaluated the cytotoxic effects of thiol-functionalized silica-coated iron oxide (Fe3O4@SiO2-SH) nanoparticles using human lung epithelial cells A549. We investigated the effect of Fe3O4@SiO2-SH nanoparticles on the cell viability, proliferation, cell cycle distribution, adhesion, apoptosis, and the orientation of the cytoskeletal networks, as well as on expression of proteins involved in cell death, cell survival, and cell adhesion. We demonstrated that exposure of A549 cells to Fe3O4@SiO2-SH nanoparticles resulted in severe disruption of the actin microfilaments and microtubule cytoskeleton and reduced the size of focal adhesions. Furthermore, cell adhesion was significantly affected as well as the phosphorylation of focal adhesion kinase (FAK), extracellular-signal-regulated kinase (ERK), and p38. Our findings highlight the need for in-depth cytotoxic evaluation of nanoparticles supporting their safer use, especially in biomedical applications.

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