Peptide modified gold nanoparticles for improved cellular uptake, nuclear transport, and intracellular retention

Nanoscale ◽  
2014 ◽  
Vol 6 (20) ◽  
pp. 12026-12033 ◽  
Author(s):  
C. Yang ◽  
J. Uertz ◽  
D. Yohan ◽  
B. D. Chithrani

A novel hyperspectral imaging technique is used to image GNPs: a combination of three peptides is used for efficient nuclear targeting and improved retention of GNPs targeted into the nucleus is shown for the first time. This is important for future cancer therapeutics as GNPs can be used as radiation dose enhancers and anticancer drug carriers.

Nanomaterials ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 396 ◽  
Author(s):  
Suhash Chavva ◽  
Sachin Deshmukh ◽  
Rajashekhar Kanchanapally ◽  
Nikhil Tyagi ◽  
Jason Coym ◽  
...  

Epigallocatechin gallate (EGCG) possesses significant antitumor activity and binds to laminin receptors, overexpressed on cancer cells, with high affinity. Gold nanoparticles (GNPs) serve as excellent drug carriers and protect the conjugated drug from enzymatic metabolization. Citrate-gold nanoparticles (C-GNPs) and EGCG-gold nanoparticles (E-GNPs) were synthesized by reduction methods and characterized with UV-visible spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering (DLS). Cytotoxicity of citrate, EGCG, C-GNPs, and E-GNPs was evaluated by the water-soluble tetrazolium salt (WST-1) assay. Nanoparticle cellular uptake studies were performed by TEM and atomic absorption spectroscopy (AAS). Dialysis method was employed to assess drug release. Cell viability studies showed greater growth inhibition by E-GNPs compared to EGCG or C-GNPs. Cellular uptake studies revealed that, unlike C-GNPs, E-GNPs were taken up more efficiently by cancerous cells than noncancerous cells. We found that E-GNP nanoformulation releases EGCG in a sustained fashion. Furthermore, data showed that E-GNPs induced more apoptosis in cancer cells compared to EGCG and C-GNPs. From the mechanistic standpoint, we observed that E-GNPs inhibited the nuclear translocation and transcriptional activity of nuclear factor-kappaB (NF-κB) with greater potency than EGCG, whereas C-GNPs were only minimally effective. Altogether, our data suggest that E-GNPs can serve as potent tumor-selective chemotoxic agents.


2021 ◽  
Author(s):  
Celina Yang

Gold nanoparticles (GNPs) have been extensively used in cancer research due to their abilities as anti-cancer drug carriers for chemotherapy and as dose enhancers in radiotherapy. Although most GNP research in the past involved cytoplasm localized GNPs, it is predicted that therapy response can be enhanced if GNPs can be effectively targeted into the nucleus. A strategy for designing a GNP-peptide complex for targeting the nucleus will be presented. Three different sequences of peptides (CKKKKKKGGAGDMFG, CGGRKKRRGRRRAP, CALNN) were conjugated onto GNPs. The first peptide was used to stabilize the complex, the second peptide to enhance uptake into the cell, while the third peptide was used to induce nuclear delivery. With nuclear targeting, more damage can be caused to the DNP of cancer cells upon irradiation. This research will establish a more successful NP-based platform that combines treatment modalities and more effectively approach cancer treatment.


Nanoscale ◽  
2020 ◽  
Vol 12 (28) ◽  
pp. 14996-15020
Author(s):  
Wei Mao ◽  
Young Ju Son ◽  
Hyuk Sang Yoo

Various gold nanoparticles have been explored as cancer therapeutics because they can be widely engineered for use as efficient drug carriers and diagnostic agents, and in photo-irradiation therapy.


2021 ◽  
Author(s):  
Celina Yang

Gold nanoparticles (GNPs) have been extensively used in cancer research due to their abilities as anti-cancer drug carriers for chemotherapy and as dose enhancers in radiotherapy. Although most GNP research in the past involved cytoplasm localized GNPs, it is predicted that therapy response can be enhanced if GNPs can be effectively targeted into the nucleus. A strategy for designing a GNP-peptide complex for targeting the nucleus will be presented. Three different sequences of peptides (CKKKKKKGGAGDMFG, CGGRKKRRGRRRAP, CALNN) were conjugated onto GNPs. The first peptide was used to stabilize the complex, the second peptide to enhance uptake into the cell, while the third peptide was used to induce nuclear delivery. With nuclear targeting, more damage can be caused to the DNP of cancer cells upon irradiation. This research will establish a more successful NP-based platform that combines treatment modalities and more effectively approach cancer treatment.


2020 ◽  
Vol 12 (7) ◽  
pp. 849-862
Author(s):  
Yuri S. Pestovsky ◽  
Teerapol Srichana

Tetrachloroaurate reduction with α-, β-, and γ-cyclodextrin at pH 10.56 was studied in this study by dual-angle dynamic light scattering and spectrophotometry. The nanoparticles were also characterized by scanning electron microscopy. In contrast with our previous study, the nanoparticles were purified by centrifugation prior to characterization. The reaction is considered to be a promising one-step method for preparation of gold nanoparticles with immobilized cyclodextrins without the need for seeding. Unlike in our previous study, the reaction mixture was boiled under reflux conditions instead of an open vial. This change sped up the reaction, and extensive aggregation was avoided. For the first time, this study demonstrated that all three cyclodextrins were able to reduce tetrachloroaurate at room temperature as well, but long incubation periods were necessary. This is the first publication discussing the mechanism of tetrachloroaurate reduction by cyclodextrins. The first stage of the reaction involved tetrachloroaurate hydrolysis despite presence of hydrochloric acid in the commercial preparation of tetrachloroauric acid (HAuCl4). Tetrachloroaurate was therefore the precursor but not the actual oxidant. The previous hypothesis on autocatalytic decarboxylation of cyclodextrins was therefore proven wrong. Particle growth was accompanied by nucleation, leading to coexistence of nanoparticles and nanoclusters. The resulting nanoparticles contained a small fraction of aggregates, probably because of sodium chloride generated from hydrochloric acid. However, besides playing this detrimental role, chloride ions facilitated nucleation by stabilizing gold intermediates. The nanoparticles solutions could be stored at least for three months, which contrasted with our previous work, where the nanoparticles were stable for only three days. For the first time, freeze-drying and reconstitution of the resulting nanoparticles were investigated, and they were shown to be free from aggregation. The synthesized gold nanoparticles are recommended for use as drug carriers.


RSC Advances ◽  
2017 ◽  
Vol 7 (17) ◽  
pp. 10333-10344 ◽  
Author(s):  
Yunli Hu ◽  
Weijun Liu ◽  
Fanhong Wu

MP-PNAAEF or MP-PNAAEM microgels exhibiting good thermo- and pH-sensitivity have been prepared for targeted delivery to FR(+) cancer cells. The DOX-loaded microgels showed higher cellular uptake by the Hela cells, but not by the L02 cells.


2017 ◽  
Vol 68 (7) ◽  
pp. 1518-1423
Author(s):  
Adina Turcu Stiolica ◽  
Mariana Popescu ◽  
Maria Viorica Bubulica ◽  
Carmen Nicoleta Oancea ◽  
Claudiu Nicolicescu ◽  
...  

Gold nanoparticles are considered the newest drug carriers for different diseases. Therefore it is appropriate continuous optimization of their preparation. In this study, gold colloids with an average size of 1 - 26 nm were obtained by the reduction of tetrachloroauric acid with trisodium citrate. The nanomaterials were characterized by UV-Vis spectroscopy and dynamic light scattering technique. In addition, zeta potential was measured for samples synthesized in order to determine the stability of the colloids. A Two-level Full Factorial design was chosen to determine the optimum set of process parameters (chloroauric acid concentration and sodium citrate concentration) and their effect on various gold nanoparticles characteristics (size and zeta potential). These effects were quantified using Design of Experiments (DoE) with 5 runs and 1 centerpoint. The selected objective and process model in this investigation are screening and interaction. Findings from this research show that to obtain particles larger than 35 nm, it is recommended to increase sodium citrate concentration, at low chloroauric acid values. These conditions will help to achieve smaller zeta potential, too.


2020 ◽  
Vol 26 (15) ◽  
pp. 1637-1649 ◽  
Author(s):  
Imran Ali ◽  
Sofi D. Mukhtar ◽  
Heyam S. Ali ◽  
Marcus T. Scotti ◽  
Luciana Scotti

Background: Nanotechnology has contributed a great deal to the field of medical science. Smart drugdelivery vectors, combined with stimuli-based characteristics, are becoming increasingly important. The use of external and internal stimulating factors can have enormous benefits and increase the targeting efficiency of nanotechnology platforms. The pH values of tumor vascular tissues are acidic in nature, allowing the improved targeting of anticancer drug payloads using drug-delivery vectors. Nanopolymers are smart drug-delivery vectors that have recently been developed and recommended for use by scientists because of their potential targeting capabilities, non-toxicity and biocompatibility, and make them ideal nanocarriers for personalized drug delivery. Method: The present review article provides an overview of current advances in the use of nanoparticles (NPs) as anticancer drug-delivery vectors. Results: This article reviews the molecular basis for the use of NPs in medicine, including personalized medicine, personalized therapy, emerging vistas in anticancer therapy, nanopolymer targeting, passive and active targeting transports, pH-responsive drug carriers, biological barriers, computer-aided drug design, future challenges and perspectives, biodegradability and safety. Conclusions: This article will benefit academia, researchers, clinicians, and government authorities by providing a basis for further research advancements.


Author(s):  
Sergey Staroverov ◽  
Sergey Kozlov ◽  
Alexander Fomin ◽  
Konstantib Gabalov ◽  
Alexey Volkov ◽  
...  

Background: The liver disease problem prompts investigators to search for new methods of liver treatment. Introduction: Silymarin (Sil) protects the liver by reducing the concentration of free radicals and the extent of damage to the cell membranes. A particularly interesting method to increase the bioavailability of Sil is to use synthesized gold nanoparticles (AuNPs) as reagents. The study considered whether it was possible to use the silymarin-AuNP conjugate as a potential liver-protecting drug. Method: AuNPs were conjugated to Sil and examine the liver-protecting activity of the conjugate. Experimental hepatitis and hepatocyte cytolysis after carbon tetrachloride actionwere used as a model system, and the experiments were conducted on laboratory animals. Result: For the first time, silymarin was conjugated to colloidal gold nanoparticles (AuNPs). Electron microscopy showed that the resultant preparations were monodisperse and that the mean conjugate diameter was 18–30 nm ± 0.5 nm (mean diameter of the native nanoparticles, 15 ± 0.5 nm). In experimental hepatitis in mice, conjugate administration interfered with glutathione depletion in hepatocytes in response to carbon tetrachloride was conducive to an increase in energy metabolism, and stimulated the monocyte–macrophage function of the liver. The results were confirmed by the high respiratory activity of the hepatocytes in cell culture. Conclusion: We conclude that the silymarin-AuNP conjugate holds promise as a liver-protecting agent in acute liver disease caused by carbon tetrachloride poisoning.


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