scholarly journals Quantum dots as targeted doxorubicin drug delivery nanosystems

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Monika Ruzycka-Ayoush ◽  
Patrycja Kowalik ◽  
Agata Kowalczyk ◽  
Piotr Bujak ◽  
Anna M. Nowicka ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Delivery ◽  
Quantum Dots ◽  
Epithelial Cells ◽  
A549 Cells ◽  
Dna Breaks ◽  
3T3 Cells ◽  
Nih 3T3 ◽  
Nih 3T3 Cells ◽  
Basal Epithelial Cells

Abstract Background Lung cancer is one of the most frequently diagnosed cancers all over the world and is also one of the leading causes of cancer-related mortality. The main treatment option for small cell lung cancer, conventional chemotherapy, is characterized by a lack of specificity, resulting in severe adverse effects. Therefore, this study aimed at developing a new targeted drug delivery (TDD) system based on Ag–In–Zn–S quantum dots (QDs). For this purpose, the QD nanocrystals were modified with 11-mercaptoundecanoic acid (MUA), L-cysteine, and lipoic acid decorated with folic acid (FA) and used as a novel TDD system for targeting doxorubicin (DOX) to folate receptors (FARs) on adenocarcinomic human alveolar basal epithelial cells (A549). NIH/3T3 cells were used as FAR-negative controls. Comprehensive physicochemical, cytotoxicity, and genotoxicity studies were performed to characterize the developed novel TDDs. Results Fourier transformation infrared spectroscopy, dynamic light scattering, and fluorescence quenching confirmed the successful attachment of FA to the QD nanocrystals and of DOX to the QD–FA nanocarriers. UV–Vis analysis helped in determining the amount of FA and DOX covalently anchored to the surface of the QD nanocrystals. Biological screening revealed that the QD–FA–DOX nanoconjugates had higher cytotoxicity in comparison to the other forms of synthesized QD samples, suggesting the cytotoxic effect of DOX liberated from the QD constructs. Contrary to the QD–MUA–FA–DOX nanoconjugates which occurred to be the most cytotoxic against A549 cells among others, no such effect was observed for NIH/3T3 cells, confirming FARs as molecular targets. In vitro scratch assay also revealed significant inhibition of A549 cell migration after treatment with QD–MUA–FA–DOX. The performed studies evidenced that at IC50 all the nanoconjugates induced significantly more DNA breaks than that observed in nontreated cells. Overall, the QD–MUA–FA–DOX nanoconjugates showed the greatest cytotoxicity and genotoxicity, while significantly inhibiting the migratory potential of A549 cells. Conclusion QD–MUA–FA–DOX nanoconjugates can thus be considered as a potential drug delivery system for the effective treatment of adenocarcinomic human alveolar basal epithelial cells.

scholarly journals Quantum dots as targeted doxorubicin drug delivery nanosystems in human lung cancer cells

2020 ◽  
Author(s):  
Monika Ruzycka ◽  
Patrycja Kowalik ◽  
Agata Kowalczyk ◽  
Piotr Bujak ◽  
Anna M. Nowicka ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Delivery ◽  
Quantum Dots ◽  
Cancer Cells ◽  
Targeted Delivery ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Dna Breaks ◽  
Folate Receptors

Abstract Background Lung cancer is one of the most frequently diagnosed cancer all over the world and a leading cancer-related mortality. The therapy of lung cancer includes surgery, chemotherapy and radiatherapy and mailny depends on the type and stage of lung cancer characterized based on WHO guidelines. Althought the conventional chemotherapy is the main treatment option for small cell lung cancer (SCLC) and a common treatment for non-SCLC it is characterized with lack of specificity resulting to severe toxicities of normal cells and harmful side effects. Therefore, targeted drug delivery (TDD) systems have been used to reduce the systemic toxicity of some conventional chemotherapies in lung cancer. Quantum dots (QDs) are fascinating nanoscale crystals that can serve as nanocarriers in TDD due to their unique physicochemical properties. Therefore, in this paper, the as-desiged QDs, Ag-In-Zn-S-based nanoconjugates for selective doxorubicin (DOX) targeting to lung cancer cells were developed. The QD nanocrystals were modified with 11-mercaptoundecanoic acid (MUA), L-cysteine (Cys) and lipoic acid (LA) used as drug carriers for targeted delivery of DOX to A549 cells through conjugated folic acid (FA) a self-navigation molecule that docks to the folate receptors on cancer cells. The comprechensive physicochemical, cytotoxicity and genotoxicity studies were performed to characterise the novel QD-based nanocaries and their anticancer cargos. Results The results from FTIR, DLS and fluorescence quenching evidenced the successful attachment of FA to the QDs nanocrystals and DOX to the QDs-FA nanocarriers. UV-vis analysis determined the amount of FA and DOX covalently anchored to the QDs nanocrystal surface. Biological screeining revealed that QDs-FA-DOX nanoconjugates showed higher cytotoxicity in comparison to other forms of the synthesized QD samples, suggesting the cytotoxic effect of liberated DOX from the QD constructs. QD-MUA-FA-DOX occurred to be the most cytotoxic against A549 cells among nanoconjugates. In vitro scratch assay also revealed significant inhibition of A549 migration only due to treatment with QD-MUA-FA-DOX. Studies evidenced that all the nanoconjugates at IC 50 induced significantly more DNA breaks than that observed in non-treated cells. All in all, significant and the greatest cytotoxicity, genotoxicity together with inhibition of migratory potential of A549 cells was observed for QD-MUA-FA-DOX. Conclusion The studies show the therapeutic efficacy of DOX-loaded QD-based cargos suggesting their promising role as novel drug delivery systems navigating to folate receptors in lung cancer cells.

Nimustine Induces DNA Breaks and Crosslinks in NIH/3T3 Cells

2013 ◽  
pp. 257-261
Author(s):  
Lin-Na Zhao ◽  
Xue-Chai Chen ◽  
Yan-Yan Zhong ◽  
Qin-Xia Hou ◽  
Ru-Gang Zhong
Keyword(s):  
Dna Breaks ◽  
3T3 Cells ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

scholarly journals Enhanced Intracellular Uptake of CdTe Quantum Dots by Conjugation of Oligopeptides

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Moon-Jeong Choi ◽  
R. Pierson ◽  
Yongmin Chang ◽  
Haiquing Guo ◽  
Inn-Kyu Kang
Keyword(s):  
Quantum Dots ◽  
Intracellular Uptake ◽  
3T3 Cells ◽  
Culture Experiment ◽  
Mean Size ◽  
Cdte Quantum Dot ◽  
Nih 3T3 ◽  
Cell Culture Experiment ◽  
Nih 3T3 Cells

Arg-Gly-Asp-Ser (RGDS), a typical membrane-permeable carrier peptide, was conjugated with mercaptoisobutyric acid-immobilized CdTe quantum dot (CTNPs) to enhance the intracellular uptake of quantum dots. Mean size of mercaptoisobutyric acid-immobilized quantum dots (37 nm) as determined by dynamic light scattering was increased up to 54 nm after RGDS immobilization. It was found, fromin vitrocell culture experiment, that fibroblast (NIH 3T3) cells were well proliferated in the presence of RGDS-conjugated quantum dots (RCTNPs), and the intracellular uptake of CTNPs and RCTNPs was studied by means of ICP and fluorescence microscopy. As a result, the RCTNPs specifically bound to the membrane of NIH 3T3 cells and almost saturated after 6 hours incubation. The amount of RCTNPs uptaken by the cells was higher than that of CTNPs, demonstrating the enhancing effect of RGDS peptide conjugation on the intracellular uptake of quantum dots (QDs).

Expression of cyclin D3 confers resistance to erlotinib

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18054-18054
Author(s):  
W. J. Petty ◽  
W. R. Voelzke ◽  
V. A. Memoli ◽  
K. H. Dragnev ◽  
J. J. Urbanic ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Cell Lines ◽  
A549 Cells ◽  
Cyclin D3 ◽  
Sensitive Cell ◽  
3T3 Cells ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

18054 Background: Transcriptional repression of cyclin D1 occurs during responses to erlotinib (E) both in vitro and in vivo. Cyclin D3 has overlapping function with cyclin D1 but has distinct transcriptional regulation. Methods: The expression of cyclin D3 was compared in E sensitive cell lines (H358, H441) and an E resistant cell line (A549). Cyclins D1, D2, and D3 were independently overexpressed in E sensitive NIH 3T3 cells by plasmid transfection. Biopsy tissues from a proof-of-principal clinical trial of E were assessed for cyclin D3 expression. Results: A549 cells were resistant to E and expressed high levels of cyclin D3 RNA and protein compared to E sensitive cell lines. Overexpression of cyclin D1 and cyclin D3 conferred partial resistance to E in NIH 3T3 cells while cyclin D2 had no significant effect. Comparison of cyclin D3 immunostaining in tumor biopsies from patients before and after treatment with E revealed an increase in the percentage of cyclin D3 expressing cells following treatment with E. Conclusions: Cyclin D3 confers resistance to E in vitro and in vivo. Drugs such as retinoids and rexinoids that target cyclin D3 expression may prove useful for enhancing sensitivity to E. No significant financial relationships to disclose.

MicroRNAs as participants in cytotoxicity of CdTe quantum dots in NIH/3T3 cells

Biomaterials ◽  
2011 ◽  
Vol 32 (15) ◽  
pp. 3807-3814 ◽  
Author(s):  
Shuchun Li ◽  
Yong Wang ◽  
Haitao Wang ◽  
Yunfei Bai ◽  
Gaofeng Liang ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Cdte Quantum Dots ◽  
3T3 Cells ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

The Products of the E5, E6, or E7 Open Reading Frames of RhPV 1 Can Individually Transform NIH 3T3 Cells or in Cotransfections with Activated Ras Can Transform Primary Rodent Epithelial Cells

Virology ◽  
1993 ◽  
Vol 196 (2) ◽  
pp. 861-867 ◽  
Author(s):  
Ronald S. Ostrow ◽  
Zhanjiang Liu ◽  
John F. Schneider ◽  
Ronald C. McGlennen ◽  
Kristina Forslund ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Open Reading Frames ◽  
3T3 Cells ◽  
Nih 3T3 ◽  
Reading Frames ◽  
Nih 3T3 Cells

Improved Therapeutic Efficacy of Topotecan Against A549 Lung Cancer Cells with Folate-targeted Topotecan Liposomes

2020 ◽  
Vol 21 (11) ◽  
pp. 902-909
Author(s):  
Jingxin Zhang ◽  
Weiyue Shi ◽  
Gangqiang Xue ◽  
Qiang Ma ◽  
Haixin Cui ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Targeted Delivery ◽  
Therapeutic Efficacy ◽  
Drug Delivery Systems ◽  
Lung Tumor ◽  
A549 Cells ◽  
Delivery Systems ◽  
Lung Cancer Cells

Background: Among all cancers, lung cancer has high mortality among patients in most of the countries in the world. Targeted delivery of anticancer drugs can significantly reduce the side effects and dramatically improve the effects of the treatment. Folate, a suitable ligand, can be modified to the surface of tumor-selective drug delivery systems because it can selectively bind to the folate receptor, which is highly expressed on the surface of lung tumor cells. Objective: This study aimed to construct a kind of folate-targeted topotecan liposomes for investigating their efficacy and mechanism of action in the treatment of lung cancer in preclinical models. Methods: We conjugated topotecan liposomes with folate, and the liposomes were characterized by particle size, entrapment efficiency, cytotoxicity to A549 cells and in vitro release profile. Technical evaluations were performed on lung cancer A549 cells and xenografted A549 cancer cells in female nude mice, and the pharmacokinetics of the drug were evaluated in female SD rats. Results: The folate-targeted topotecan liposomes were proven to show effectiveness in targeting lung tumors. The anti-tumor effects of these liposomes were demonstrated by the decreased tumor volume and improved therapeutic efficacy. The folate-targeted topotecan liposomes also lengthened the topotecan blood circulation time. Conclusion: The folate-targeted topotecan liposomes are effective drug delivery systems and can be easily modified with folate, enabling the targeted liposomes to deliver topotecan to lung cancer cells and kill them, which could be used as potential carriers for lung chemotherapy.

scholarly journals Effects of Aspergillus fumigatus Conidia on Apoptosis and Proliferation in an In Vitro Model of the Lung Microenvironment

2021 ◽  
Vol 9 (7) ◽  
pp. 1435
Author(s):  
Hisako Kushima ◽  
Toshiyuki Tsunoda ◽  
Taichi Matsumoto ◽  
Yoshiaki Kinoshita ◽  
Koichi Izumikawa ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Epithelial Cells ◽  
Pulmonary Fibrosis ◽  
Aspergillus Fumigatus ◽  
Rna Sequencing ◽  
A549 Cells ◽  
Western Blots ◽  
Mesenchymal Transition ◽  
Expression Of Genes ◽  
Nih 3T3

Background/Aim: Aspergillus is often detected in respiratory samples from patients with chronic respiratory diseases, including pulmonary fibrosis, suggesting that it can easily colonize the airways. To determine the role of Aspergillus colonization in pulmonary fibrosis, we cultured human lung epithelial A549 cells or murine embryo fibroblast NIH/3T3 cells with Aspergillus conidia in 3D floating culture representing the microenvironment. Materials and Methods: Cells were cultured in two-dimensional (2D) and three-dimensional floating (3DF) culture with heat-inactivated Aspergillus fumigatus (AF) 293 conidia at an effector-to-target cell ratio of 1:10 (early-phase model) and 1:100 (colonization model), and RNA-sequencing and Western blots (WB) were performed. Results: AF293 conidia reduced A549 cell growth in 2D and 3DF cultures and induced apoptosis in A549 spheroids in 3DF culture. RNA-sequencing revealed the increased expression of genes associated with interferon-mediated antiviral responses including MX dymamin-like GTPase 1 (MX1). Interestingly, the decreased expression of genes associated with the cell cycle was observed with a high concentration of AF293 conidia. WB revealed that epithelial-mesenchymal transition was not involved. Notably, AF293 conidia increased NIH/3T3 growth only in 3DF culture without inducing an apoptotic reaction. RNA-sequencing revealed the increased expression of genes associated with interferon signalling, including MX2; however, the decreased expression of genes associated with the cell cycle was not observed. Conclusions: AF affects both apoptosis of epithelial cells and the growth of fibroblasts. A deeper understanding of the detailed mechanisms underlying Aspergillus-mediated signaling pathway in epithelial cells and fibroblasts will help us to understand the lung microenvironment.

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