Optimization and Characterization of Protein Nanoparticles for the Targeted and Smart Delivery of Cytochrome c to Non-Small Cell Lung Carcinoma

Barcelo‐Bovea, Vanessa; Dominguez-Martinez, Irivette; Joaquin-Ovalle, Freisa; Amador, Luis A.; Castro-Rivera, Elizabeth; Medina-Álvarez, Kristofer; McGoron, Anthony J.; Griebenow, Kai; Ferrer-Acosta, Yancy

doi:10.20944/preprints202004.0221.v1

Cited by 7 publications

(1 citation statement)

References 37 publications

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“…Thus, formulations for its intracellular delivery need to be devised [ 41 ]. Previously, several groups have shown that the cytoplasmic delivery of cytochrome c can be achieved either via conjugation to ligands of cell surface receptors, such as transferrin and folate, or by its encapsulation in polymers [ 42 , 43 , 44 ].…”

Section: Introductionmentioning

confidence: 99%

Membrane-Interacting DNA Nanotubes Induce Cancer Cell Death

Kocabey

Schneiter

et al. 2021

Nanomaterials

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DNA nanotechnology offers to build nanoscale structures with defined chemistries to precisely position biomolecules or drugs for selective cell targeting and drug delivery. Owing to the negatively charged nature of DNA, for delivery purposes, DNA is frequently conjugated with hydrophobic moieties, positively charged polymers/peptides and cell surface receptor-recognizing molecules or antibodies. Here, we designed and assembled cholesterol-modified DNA nanotubes to interact with cancer cells and conjugated them with cytochrome c to induce cancer cell apoptosis. By flow cytometry and confocal microscopy, we observed that DNA nanotubes efficiently bound to the plasma membrane as a function of the number of conjugated cholesterol moieties. The complex was taken up by the cells and localized to the endosomal compartment. Cholesterol-modified DNA nanotubes, but not unmodified ones, increased membrane permeability, caspase activation and cell death. Irreversible inhibition of caspase activity with a caspase inhibitor, however, only partially prevented cell death. Cytochrome c-conjugated DNA nanotubes were also efficiently taken up but did not increase the rate of cell death. These results demonstrate that cholesterol-modified DNA nanotubes induce cancer cell death associated with increased cell membrane permeability and are only partially dependent on caspase activity, consistent with a combined form of apoptotic and necrotic cell death. DNA nanotubes may be further developed as primary cytotoxic agents, or drug delivery vehicles, through cholesterol-mediated cellular membrane interactions and uptake.

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Section: Introductionmentioning

confidence: 99%

Membrane-Interacting DNA Nanotubes Induce Cancer Cell Death

Kocabey

Schneiter

et al. 2021

Nanomaterials

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Deferasirox’s Anti-Chemoresistance and Anti-Metastatic Effect on Non-Small Cell Lung Carcinoma

Delgado,

Torres-Sanchez,

Perez

et al. 2024

Biomedicines

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Clinically approved iron chelators, originally designed to address iron overload disorders, have emerged as potential anticancer agents. Deferasirox (Def), a tridentate iron chelator, has demonstrated antiproliferative effects in cancer. Background/Objectives: This study aims to elucidate the mechanism of action of Def and its impact on non-small cell lung carcinoma (NSCLC). Methods: NSCLC A549 cells were treated with Def to assess cytotoxicity, the effect on nuclear and mitochondrial pathways, and iron-containing proteins and genes to evaluate anti-metastasis and chemoresistance. A lung carcinoma mouse model was used for in vivo studies. Results: Our findings revealed that Def induced cytotoxicity, effectively chelated intracellular iron, and triggered apoptosis through the increase in phosphatidylserine externalization and caspase 3 activity. Additionally, Def caused G0/G1 cell cycle arrest by downregulating the ribonucleotide reductase catalytic subunit. Furthermore, Def perturbed mitochondrial function by promoting the production of reactive oxygen species and the inhibition of glutathione as a measurement of ferroptosis activation. Def demonstrated inhibitory effects on cell migration in scratch assays, which was supported by the upregulation of n-myc downstream-regulated gene 1 and downregulation of the epidermal growth factor receptor protein. Also, Def downregulated one of the main markers of chemoresistance, the ABCB1 gene. In vivo experiments using a lung carcinoma mouse model showed that Def treatment did not affect the animal’s body weight and showed a significant decrease in tumor growth. Conclusions: This investigation lays the groundwork for unraveling Def action’s molecular targets and mechanisms in lung carcinoma, particularly within iron-related pathways, pointing out its anti-metastasis and anti-chemoresistance effect.

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The Impact of Long Noncoding RNAs in Tissue Regeneration and Senescence

Tavares e Silva,

Pessoa,

Nóbrega-Pereira

et al. 2024

Cells

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Overcoming senescence with tissue engineering has a promising impact on multiple diseases. Here, we provide an overview of recent studies in which cellular senescence was inhibited through the up/downregulation of specific lncRNAs. This approach prevented senescence in the bones, joints, nervous system, heart, and blood vessels, with a potential impact on regeneration and the prevention of osteoarthritis and osteoporosis, as well as neurodegenerative and cardiovascular diseases. Senescence of the skin and liver could also be prevented through the regulation of cellular levels of specific lncRNAs, resulting in the rejuvenation of cells from these organs and their potential protection from disease. From these exciting achievements, which support tissue regeneration and are not restricted to stem cells, we propose lncRNA regulation through RNA or gene therapies as a prospective preventive and therapeutic approach against aging and multiple aging-related diseases.

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Optimization and Characterization of Protein Nanoparticles for the Targeted and Smart Delivery of Cytochrome c to Non-Small Cell Lung Carcinoma

Cited by 7 publications

References 37 publications

Membrane-Interacting DNA Nanotubes Induce Cancer Cell Death

Membrane-Interacting DNA Nanotubes Induce Cancer Cell Death

Deferasirox’s Anti-Chemoresistance and Anti-Metastatic Effect on Non-Small Cell Lung Carcinoma

The Impact of Long Noncoding RNAs in Tissue Regeneration and Senescence

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