Diselenolane‐Mediated Cellular Uptake: Efficient Cytosolic Delivery of Probes, Peptides, Proteins, Artificial Metalloenzymes and Protein‐Coated Quantum Dots

Nanotechnology-based drug delivery provides a promising area for improving the efficacy of cancer treatments. Therefore, we investigate the potential of using quantum dots (QDs) as drug carriers for antitumor unsymmetrical bisacridine derivatives (UAs) to cancer cells. We examine the influence of QD–UA hybrids on the cellular uptake, internalization (Confocal Laser Scanning Microscope), and the biological response (flow cytometry and light microscopy) in lung H460 and colon HCT116 cancer cells. We show the time-dependent cellular uptake of QD–UA hybrids, which were more efficiently retained inside the cells compared to UAs alone, especially in H460 cells, which could be due to multiple endocytosis pathways. In contrast, in HCT116 cells, the hybrids were taken up only by one endocytosis mechanism. Both UAs and their hybrids induced apoptosis in H460 and HCT116 cells (to a greater extent in H460). Cells which did not die underwent senescence more efficiently following QDs–UAs treatment, compared to UAs alone. Cellular senescence was not observed in HCT116 cells following treatment with both UAs and their hybrids. Importantly, QDgreen/red themselves did not provoke toxic responses in cancer or normal cells. In conclusion, QDs are good candidates for targeted UA delivery carriers to cancer cells while protecting normal cells from toxic drug activities.

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Cellular Uptake and Cytosolic Delivery of a Cyclic Cystine Knot Scaffold

ACS Chemical Biology ◽

10.1021/acschembio.0c00297 ◽

2020 ◽

Vol 15 (6) ◽

pp. 1650-1661 ◽

Cited By ~ 1

Author(s):

Huawu Yin ◽

Yen-Hua Huang ◽

Kirsten Deprey ◽

Nicholas D. Condon ◽

Joshua A. Kritzer ◽

...

Keyword(s):

Cellular Uptake ◽

Cystine Knot ◽

Cytosolic Delivery

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Nano-Bio Interaction between Blood Plasma Proteins and Water-Soluble Silicon Quantum Dots with Enabled Cellular Uptake and Minimal Cytotoxicity

Nanomaterials ◽

10.3390/nano10112250 ◽

2020 ◽

Vol 10 (11) ◽

pp. 2250

Author(s):

Shanmugavel Chinnathambi ◽

Nobutaka Hanagata ◽

Tomohiko Yamazaki ◽

Naoto Shirahata

Keyword(s):

Quantum Dots ◽

Blood Plasma ◽

Cellular Uptake ◽

Plasma Proteins ◽

Protein Corona ◽

Water Soluble ◽

Pluronic F127 ◽

Infrared Light ◽

Spectral Window ◽

Blood Plasma Proteins

A better understanding of the compatibility of water-soluble semiconductor quantum dots (QDs) upon contact with the bloodstream is important for biological applications, including biomarkers working in the first therapeutic spectral window for deep tissue imaging. Herein, we investigated the conformational changes of blood plasma proteins during the interaction with near-infrared light-emitting nanoparticles, consisting of Pluronic F127 shells and cores comprised of assembled silicon QDs terminated with decane monolayers. Albumin and transferrin have high quenching constants and form a hard protein corona on the nanoparticle. In contrast, fibrinogen has low quenching constants and forms a soft protein corona. A circular dichroism (CD) spectrometric study investigates changes in the protein’s secondary and tertiary structures with incremental changes in the nanoparticle concentrations. As expected, the addition of nanoparticles causes the denaturation of the plasma proteins. However, it is noteworthy that the conformational recovery phenomena are observed for fibrinogen and transferrin, suggesting that the nanoparticle does not influence the ordered structure of proteins in the bloodstream. In addition, we observed enabled cellular uptake (NIH3T3 Fibroblasts) and minimal cytotoxicity using different cell lines (HeLa, A549, and NIH3T3). This study offers a basis to design QDs without altering the biomacromolecule’s original conformation with enabled cellular uptake with minimal cytotoxicity.

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Non-specific cellular uptake of surface-functionalized quantum dots

Nanotechnology ◽

10.1088/0957-4484/21/28/285105 ◽

2010 ◽

Vol 21 (28) ◽

pp. 285105 ◽

Cited By ~ 89

Author(s):

T A Kelf ◽

V K A Sreenivasan ◽

J Sun ◽

E J Kim ◽

E M Goldys ◽

...

Keyword(s):

Quantum Dots ◽

Cellular Uptake

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Cationic poly(amidoamine) promotes cytosolic delivery of bovine RNase A in melanoma cells, while maintaining its cellular toxicity

Journal of Materials Chemistry B ◽

10.1039/c4tb02065k ◽

2015 ◽

Vol 3 (31) ◽

pp. 6501-6508 ◽

Cited By ~ 4

Author(s):

Julie L. N. Dubois ◽

Nathalie Lavignac

Keyword(s):

Cell Death ◽

Cellular Uptake ◽

Melanoma Cells ◽

Rnase A ◽

Wild Type ◽

Cellular Toxicity ◽

Cytosolic Delivery

Poly(amidoamine)s enhance cellular uptake of wild-type RNase A in B16F1 melanoma cells and help its cytosolic delivery, inducing increased cell death.

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Nona-Arginine Facilitates Delivery of Quantum Dots into Cells via Multiple Pathways

Journal of Biomedicine and Biotechnology ◽

10.1155/2010/948543 ◽

2010 ◽

Vol 2010 ◽

pp. 1-11 ◽

Cited By ~ 17

Author(s):

Yi Xu ◽

Betty Revon Liu ◽

Han-Jung Lee ◽

Katie B. Shannon ◽

Jeffrey G. Winiarz ◽

...

Keyword(s):

Quantum Dots ◽

Cellular Uptake ◽

Metabolic Inhibitors ◽

Cellular Internalization ◽

Caveolin 1 ◽

Dependent Process ◽

A Cell ◽

Low Efficiency ◽

Rnai Technique ◽

Energy Dependent

Semiconductor quantum dots (QDs) have recently been used to deliver and monitor biomolecules, such as drugs and proteins. However, QDs alone have a low efficiency of transport across the plasma membrane. In order to increase the efficiency, we used synthetic nona-arginine (SR9), a cell-penetrating peptide, to facilitate uptake. We found that SR9 increased the cellular uptake of QDs in a noncovalent binding manner between QDs and SR9. Further, we investigated mechanisms of QD/SR9 cellular internalization. Low temperature and metabolic inhibitors markedly inhibited the uptake of QD/SR9, indicating that internalization is an energy-dependent process. Results from both the pathway inhibitors and the RNA interference (RNAi) technique suggest that cellular uptake of QD/SR9 is predominantly a lipid raft-dependent process mediated by macropinocytosis. However, involvement of clathrin and caveolin-1 proteins in transducing QD/SR9 across the membrane cannot be completely ruled out.

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Cellular Uptake and Cytosolic Delivery of a Cyclic Cystine Knot Scaffold

10.26434/chemrxiv.11860155 ◽

2020 ◽

Author(s):

Huawu Yin ◽

Yen-Hua Huang ◽

Kirsten Deprey ◽

Nicholas Condon ◽

Joshua Kritzer ◽

...

Keyword(s):

Cellular Uptake ◽

Therapeutic Potential ◽

Hydrophobic Amino Acid ◽

Kalata B1 ◽

Cytosolic Delivery ◽

Intracellular Proteins ◽

Macrocyclic Peptides ◽

Low Efficiency ◽

Further Development ◽

Stable Structures

Cyclotides are macrocyclic peptides that have exceptionally stable structures and been reported to penetrate cells, making them promising scaffolds for the delivery of peptide inhibitory sequences to target intracellular proteins. However, their cellular uptake and cytosolic localization have been poorly understood until now, which has limited their therapeutic potential. In this study, the recently developed chloroalkane penetration assay was combined with established assays to characterize the cellular uptake and cytosolic delivery of the prototypic cyclotide, kalata B1. We show that kalata B1 enters the cytosol at low efficiency, but introducing various epitopes, including a single hydrophobic amino acid, into its loop 6 significantly improved its cytosolic delivery. Our results provide a foundation for the further development of a structurally unique class of scaffolds for the delivery of therapeutic cargoes into cells.<br>

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