scholarly journals Cellular Uptake and Cytosolic Delivery of a Cyclic Cystine Knot Scaffold

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>

Cellular Uptake and Cytosolic Delivery of a Cyclic Cystine Knot Scaffold

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>

scholarly journals Dietary Curcumin: Correlation between Bioavailability and Health Potential

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2147 ◽  
Author(s):  
Michele Dei Cas ◽  
Riccardo Ghidoni
Keyword(s):  
Small Intestine ◽  
Cellular Uptake ◽  
Oral Delivery ◽  
Therapeutic Potential ◽  
Pharmacokinetic Profile ◽  
Yellow Pigment ◽  
The Body ◽  
Anti Cancer ◽  
Poor Absorption ◽  
Oral Delivery Systems

The yellow pigment curcumin, extracted from turmeric, is a renowned polyphenol with a broad spectrum of health properties such as antioxidant, anti-inflammatory, anti-cancer, antidiabetic, hepatoprotective, anti-allergic, anti-dermatophyte, and neuroprotective. However, these properties are followed by a poor pharmacokinetic profile which compromises its therapeutic potential. The association of low absorption by the small intestine and the extensive reductive and conjugative metabolism in the liver dramatically weakens the oral bioavailability. Several strategies such as inhibition of curcumin metabolism with adjuvants as well as novel solid and liquid oral delivery systems have been tried to counteract curcumin poor absorption and rapid elimination from the body. Some of these drug deliveries can successfully enhance the solubility, extending the residence in plasma, improving the pharmacokinetic profile and the cellular uptake.

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

2019 ◽  
Vol 25 (16) ◽  
pp. 4047-4051 ◽  
Author(s):  
Eline Bartolami ◽  
Dimitris Basagiannis ◽  
Lili Zong ◽  
Rémi Martinent ◽  
Yasunori Okamoto ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Cellular Uptake ◽  
Cytosolic Delivery ◽  
Artificial Metalloenzymes

scholarly journals Cellular Uptake and Cytosolic Delivery of a Cyclic Cystine Knot Scaffold

2020 ◽  
Vol 15 (6) ◽  
pp. 1650-1661 ◽  
Author(s):  
Huawu Yin ◽  
Yen-Hua Huang ◽  
Kirsten Deprey ◽  
Nicholas D. Condon ◽  
Joshua A. Kritzer ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Cystine Knot ◽  
Cytosolic Delivery

A further development of the QNAR model to predict the cellular uptake of nanoparticles by pancreatic cancer cells

2018 ◽  
Vol 112 ◽  
pp. 571-580 ◽  
Author(s):  
Feng Luan ◽  
Lili Tang ◽  
Lihong Zhang ◽  
Shuang Zhang ◽  
Maykel Cruz Monteagudo ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cellular Uptake ◽  
Pancreatic Cancer Cells ◽  
Further Development

scholarly journals Energy industry of the Republic of Buryatia: current state and prerequisites for further development

2019 ◽  
Vol 77 ◽  
pp. 03005
Author(s):  
Gennadiy Borisov ◽  
Zorikto Dondokov
Keyword(s):  
Development Strategy ◽  
Energy Security ◽  
Thermal Power ◽  
Energy System ◽  
Gas Processing ◽  
Energy Complex ◽  
The Republic ◽  
Low Efficiency ◽  
Main Activity ◽  
Further Development

The article contains the results of a study of the state of the fuel and energy complex (FEC) of the Republic of Buryatia. The role of fuel and energy complex in the economy of the republic is analyzed in the article. The main problems, the solution of which is necessary for further development of the industry, including energy security and low efficiency of heat and power production in the power system, are identified by the author. The tasks of development of transboundary interaction with the energy system of Mongolia are defined. Possible options for gasification of Buryatia were studied. To ensure increased energy security of the Republic of Buryatia and the efficiency of the Buryat energy system, the main activity is the continuation of the construction of Ulan-Ude Thermal Power Station-2. The necessity of actualization of the development strategy of the fuel and energy complex of the Baikal region based on the diversification of the fuel and energy balance due to gasification, the development of gas processing and gas chemistry, the use of non-traditional and renewable types of energy is substantiated.

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

2015 ◽  
Vol 3 (31) ◽  
pp. 6501-6508 ◽  
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.

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

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
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.

Therapeutic Potential of Trp-Rich Engineered Amphiphiles by Single Hydrophobic Amino Acid End-Tagging

2019 ◽  
Vol 11 (47) ◽  
pp. 43820-43834 ◽  
Author(s):  
Jing Song ◽  
Jiajun Wang ◽  
Na Zhan ◽  
Taotao Sun ◽  
Weikang Yu ◽  
...  
Keyword(s):  
Amino Acid ◽  
Therapeutic Potential ◽  
Hydrophobic Amino Acid

scholarly journals Photochemical Internalization: Light Paves Way for New Cancer Chemotherapies and Vaccines

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 165 ◽  
Author(s):  
Lara Šošić ◽  
Pål Kristian Selbo ◽  
Zuzanna K. Kotkowska ◽  
Thomas M. Kündig ◽  
Anders Høgset ◽  
...  
Keyword(s):  
Phase I ◽  
Therapeutic Potential ◽  
Virus Antigen ◽  
Chemotherapeutic Agents ◽  
Eligibility Criteria ◽  
Ongoing Research ◽  
Clinical Phase ◽  
Photochemical Internalization ◽  
Cancer Remission ◽  
Further Development

Photochemical internalization (PCI) is a further development of photodynamic therapy (PDT). In this report, we describe PCI as a potential tool for cellular internalization of chemotherapeutic agents or antigens and systematically review the ongoing research. Eighteen published papers described the pre-clinical and clinical developments of PCI-mediated delivery of chemotherapeutic agents or antigens. The studies were screened against pre-defined eligibility criteria. Pre-clinical studies suggest that PCI can be effectively used to deliver chemotherapeutic agents to the cytosol of tumor cells and, thereby, improve treatment efficacy. One Phase-I clinical trial has been conducted, and it demonstrated that PCI-mediated bleomycin treatment was safe and identified tolerable doses of the photosensitizer disulfonated tetraphenyl chlorin (TPCS2a). Likewise, PCI was pre-clinically shown to mediate major histocompatibility complex (MHC) class I antigen presentation and generation of tumor-specific cytotoxic CD8+ T-lymphocytes (CTL) and cancer remission. A first clinical Phase I trial with the photosensitizer TPCS2a combined with human papilloma virus antigen (HPV) was recently completed and results are expected in 2020. Hence, photosensitizers and light can be used to mediate cytosolic delivery of endocytosed chemotherapeutics or antigens. While the therapeutic potential in cancer has been clearly demonstrated pre-clinically, further clinical trials are needed to reveal the true translational potential of PCI in humans.

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