Citrate-capped gold nanoparticles with a diameter of 14nm alter the expression of genes associated with stress response, cytoprotection and lipid metabolism in CaCo-2 cells

2021 ◽  
Author(s):  
Adedoja Dorcas Wusu ◽  
Nicole Remaliah Samantha Sibuyi ◽  
Koena Leah Moabelo ◽  
Mediline Goboza ◽  
Abram Madiehe ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Drug Delivery ◽  
Gold Nanoparticles ◽  
Lipid Metabolism ◽  
Antioxidant Response ◽  
Drug Delivery Vehicles ◽  
Cellular Processes ◽  
Expression Of Genes ◽  
Treatment Conditions ◽  
Delivery Vehicles

Abstract Advancements in nanotechnology have provided insight into the unique opportunities for the application of nanomaterials such as gold nanoparticles (AuNPs) in medicine due to their remarkable properties, which includes low toxicity, large surface area, and the ease of synthesis and conjugation to other molecules. Therefore, AuNPs are often preferred for bio-applications. Citrate-capped AuNPs (cAuNPs) have been reported to be non-cytotoxic and are used in numerous studies as drug delivery vehicles to treat various diseases. However, the limitations of bioassays often used to assess the toxicity of AuNPs have been well documented. Herein, we investigate the cytotoxicity of 14nm cAuNPs in the human colorectal adenocarcinoma (Caco-2) cell line. Treatment conditions (i.e., dose and exposure time) that were established to be non-toxic to Caco-2 cells were used to investigate the effect of cAuNPs on the expression of a Qiagen panel of 86 genes involved in cytotoxicity. Out of 86 studied, 23 genes were differentially expressed. Genes involved in oxidative stress and antioxidant response, endoplasmic reticulum (ER) stress and unfolded protein response (UPR), heat shock response (HSR), and lipid metabolism were more affected than others. While low concentrations of 14nm cAuNPs was not cytotoxic and did not cause cell death, cells treated with these nanoparticles experienced ER and oxidative stress, resulting in the activation of cytoprotective cellular processes. Additionally, several genes involved in lipid metabolism were also affected. Therefore, 14nm cAuNPs can safely be used as drug delivery vehicles at low doses.

scholarly journals Gold–Protein Composite Nanoparticles for Enhanced X-ray Interactions: A Potential Formulation for Triggered Release

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1407
Author(s):  
Courtney van Ballegooie ◽  
Alice Man ◽  
Alessia Pallaoro ◽  
Marcel Bally ◽  
Byron D. Gates ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Gold Nanoparticles ◽  
External Beam Radiation ◽  
Therapeutic Effects ◽  
Delivery Vehicle ◽  
Triggered Release ◽  
Gold Particles ◽  
Drug Delivery Vehicles ◽  
Delivery Vehicles ◽  
Zein Protein

Drug-delivery vehicles have been used extensively to modulate the biodistribution of drugs for the purpose of maximizing their therapeutic effects while minimizing systemic toxicity. The release characteristics of the vehicle must be balanced with its encapsulation properties to achieve optimal delivery of the drug. An alternative approach is to design a delivery vehicle that preferentially releases its contents under specific endogenous (e.g., tissue pH) or exogenous (e.g., applied temperature) stimuli. In the present manuscript, we report on a novel delivery system with potential for triggered release using external beam radiation. Our group evaluated Zein protein as the basis for the delivery vehicle and used radiation as the exogenous stimulus. Proteins are known to react with free radicals, produced during irradiation in aqueous suspensions, leading to aggregation, fragmentation, amino acid modification, and proteolytic susceptibility. Additionally, we incorporated gold particles into the Zein protein matrix to create hybrid Zein–gold nanoparticles (ZAuNPs). Zein-only nanoparticles (ZNPs) and ZAuNPs were subsequently exposed to kVp radiation (single dose ranging from 2 to 80 Gy; fractionated doses of 2 Gy delivered 10 times) and characterized before and after irradiation. Our data indicated that the presence of gold particles within Zein particles was correlated with significantly higher levels of alterations to the protein, and was associated with higher rates of release of the encapsulated drug compound, Irinotecan. The aggregate results demonstrated a proof-of-principle that radiation can be used with gold nanoparticles to modulate the release rates of protein-based drug-delivery vehicles, such as ZNPs.

Gold nanoparticles and gold nanoparticle-conjugates for delivery of therapeutic molecules. Progress and challenges

2014 ◽  
Vol 2 (27) ◽  
pp. 4204-4220 ◽  
Author(s):  
I. Fratoddi ◽  
I. Venditti ◽  
C. Cametti ◽  
M. V. Russo
Keyword(s):  
Drug Delivery ◽  
Gold Nanoparticles ◽  
Cancer Cells ◽  
Gold Nanoparticle ◽  
Drug Delivery Vehicles ◽  
Selective Targeting ◽  
Therapeutic Molecules ◽  
Delivery Vehicles

Gold nanoparticles and their conjugates as drug delivery vehicles for selective targeting of cancer cells.

Nanoparticles for Cellular Drug Delivery: Mechanisms and Factors Influencing Delivery

2006 ◽  
Vol 6 (9) ◽  
pp. 2651-2663 ◽  
Author(s):  
Mahesh D. Chavanpatil ◽  
Ayman Khdair ◽  
Jayanth Panyam
Keyword(s):  
Drug Delivery ◽  
Polymeric Nanoparticles ◽  
Reticuloendothelial System ◽  
Drug Delivery Vehicles ◽  
Cellular Processes ◽  
Physicochemical Factors ◽  
Surface Ligand ◽  
Delivery Vehicles ◽  
Nanoparticle Formulation ◽  
Specific Ligand

Polymeric nanoparticles have demonstrated enormous potential as cellular drug delivery vehicles. Nanoparticles improve drug's stability as well as its availability and retention at the target intracellular site of action. Therapeutic efficacy of nanoparticles can be further enhanced by conjugating specific ligands to nanoparticle surface. Ligand conjugation can also be used to favorably modify the intracellular disposition of nanoparticles. A number of ligands are available for this purpose; use of a specific ligand depends on the target cell, the material used for nanoparticle formulation, and the chemistry available for ligand-nanoparticle conjugation. Cellular drug delivery using nanoparticles is also affected by clearance through the reticuloendothelial system. In this paper, we review the recent progress on our understanding of physicochemical factors that affect the cellular uptake of nanoparticles and the different cellular processes that could be exploited to enhance nanoparticle uptake into cells.

scholarly journals Hyaluronic Acid-Based Gold Nanoparticles for the Topical Delivery of Therapeutics to the Retina and the Retinal Pigment Epithelium

Polymers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 3324
Author(s):  
Amine Laradji ◽  
Bedia Karakocak ◽  
Alexander Kolesnikov ◽  
Vladimir Kefalov ◽  
Nathan Ravi
Keyword(s):  
Drug Delivery ◽  
Gold Nanoparticles ◽  
Hyaluronic Acid ◽  
Inductively Coupled Plasma ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Posterior Segment ◽  
Drug Delivery Vehicles ◽  
Inductively Coupled ◽  
Delivery Vehicles

The ocular immune privilege is a phenomenon brought about by anatomical and physiological barriers to shield the eye from immune and inflammation responses. While this phenomenon is beneficial for eyes protection, it is, at the same time, a hindrance for drug delivery to the posterior segment of the eye to treat retinal diseases. Some ocular barriers can be bypassed by intravitreal injections, but these are associated with several side effects and patient noncompliance, especially when frequent injections are required. As an alternative, applying drugs as an eye drop is preferred due to the safety and ease. This study investigated the possible use of topically-applied hyaluronic acid-coated gold nanoparticles as drug delivery vehicles to the back of the eye. The coated gold nanoparticles were topically applied to mouse eyes, and results were compared to topically applied uncoated gold nanoparticles and phosphate-buffered saline (PBS) solution. Retina sections from these mice were then analyzed using fluorescence microscopy, inductively coupled plasma mass spectrometry (ICP-MS), and transmission electron microscopy (TEM). All characterization techniques used in this study suggest that hyaluronic acid-coated gold nanoparticles have higher distribution in the posterior segment of the eye than uncoated gold nanoparticles. Electroretinogram (ERG) analysis revealed that the visual function of mice receiving the coated gold nanoparticles was not affected, and these nanoparticles can, therefore, be applied safely. Together, our results suggest that hyaluronic acid-coated gold nanoparticles constitute potential drug delivery vehicles to the retina when applied noninvasively as an eye drop.

Dendrimers: General Aspects, Applications and Structural Exploitations as Prodrug/Drug-delivery Vehicles in Current Medicine

2018 ◽  
Vol 18 (5) ◽  
pp. 439-457 ◽  
Author(s):  
Merina Mariyam ◽  
Kajal Ghosal ◽  
Sabu Thomas ◽  
Nandakumar Kalarikkal ◽  
Mahima S. Latha
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Vehicles ◽  
Delivery Vehicles ◽  
General Aspects

Novel Phospholipid-Based Labrasol Nanomicelles Loaded Flavonoids for Oral Delivery with Enhanced Penetration and Anti-Brain Tumor Efficiency

2020 ◽  
Vol 17 (3) ◽  
pp. 229-245
Author(s):  
Gang Wang ◽  
Junjie Wang ◽  
Rui Guan
Keyword(s):  
Drug Delivery ◽  
Brain Tumor ◽  
Oral Delivery ◽  
Safe Delivery ◽  
Drug Delivery Vehicles ◽  
Therapeutic Benefits ◽  
Delivery Vehicles ◽  
The Brain

Background: Owing to the rich anticancer properties of flavonoids, there is a need for their incorporation into drug delivery vehicles like nanomicelles for safe delivery of the drug into the brain tumor microenvironment. Objective: This study, therefore, aimed to prepare the phospholipid-based Labrasol/Pluronic F68 modified nano micelles loaded with flavonoids (Nano-flavonoids) for the delivery of the drug to the target brain tumor. Methods: Myricetin, quercetin and fisetin were selected as the initial drugs to evaluate the biodistribution and acute toxicity of the drug delivery vehicles in rats with implanted C6 glioma tumors after oral administration, while the uptake, retention, release in human intestinal Caco-2 cells and the effect on the brain endothelial barrier were investigated in Human Brain Microvascular Endothelial Cells (HBMECs). Results: The results demonstrated that nano-flavonoids loaded with myricetin showed more evenly distributed targeting tissues and enhanced anti-tumor efficiency in vivo without significant cytotoxicity to Caco-2 cells and alteration in the Trans Epithelial Electric Resistance (TEER). There was no pathological evidence of renal, hepatic or other organs dysfunction after the administration of nanoflavonoids, which showed no significant influence on cytotoxicity to Caco-2 cells. Conclusion: In conclusion, Labrasol/F68-NMs loaded with MYR and quercetin could enhance antiglioma effect in vitro and in vivo, which may be better tools for medical therapy, while the pharmacokinetics and pharmacodynamics of nano-flavonoids may ensure optimal therapeutic benefits.

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