ABSTRACT
AIM: The objective of this research was to estimate the dose distribution delivered by radioactive gold nanoparticles (198AuNPs or 199AuNPs) to the tumor inside the human prostate as well as to normal tissues surrounding the tumor using the Monte-Carlo N-Particle code (MCNP-6.1.1 code). BACKGROUND: Radioactive gold nanoparticles are emerging as promising agents for cancer therapy and are being investigated to treat prostate cancer in animals. In order to use them as a new therapeutic modality to treat human prostate cancer, accurate radiation dosimetry simulations are required to estimate the energy deposition in the tumor and surrounding tissue and to establish the course of therapy for the patient. MATERIALS AND METHODS: A simple geometrical model of a human prostate was used, and the dose deposited by 198AuNPs or 199AuNPs to the tumor within the prostate as well as to the healthy tissue surrounding the prostate was calculated using the MCNP code. Water and A-150 TEP phantoms were used to simulate the soft and tumor tissues. RESULTS: The results showed that the dose due to 198AuNPs or 199AuNPs, which are distributed homogenously in the tumor, had a maximal value in the tumor region and then rapidly decreased toward the prostate-tumor interface and surrounding organs. However, the dose deposited by 198Au is significantly higher than the dose deposited by 199Au in the tumor region as well as normal tissues. CONCLUSIONS: According to the MCNP results, 198AuNPs are a promising modality to treat prostate cancer and other cancers and 199AuNPs could be used for imaging purposes.
ABSTRACT
In our efforts to develop new approaches to treat and prevent human vascular diseases, we report herein our results on the proliferation and migration of human smooth muscles cells (SMCs) and endothelial cells (ECs) using epigallocatechin-3-gallate conjugated gold nanoparticles (EGCg-AuNPs) as possible alternatives to drug coated stents. Detailed in vitro stability studies of EGCg-AuNPs in various biological fluids, affinity and selectivity towards SMCs and ECs have been investigated. The EGCg-AuNPs showed selective inhibitory efficacy toward the migration of SMCs. However, the endothelial cells remained unaffected under similar experimental conditions. The cellular internalization studies have indicated that EGCg-AuNPs internalize into the SMCs and ECs within short periods of time through laminin receptor mediated endocytosis mode. Favorable toxicity profiles and selective affinity toward SMCs and ECs suggest that EGCg-AuNPs may provide attractive alternatives to drug coated stents and therefore offer new therapeutic approaches in treating cardiovascular diseases.
Subject(s)
Antioxidants/administration & dosage , Antioxidants/pharmacology , Catechin/analogs & derivatives , Drug Carriers/chemistry , Gold/chemistry , Metal Nanoparticles/chemistry , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/pharmacokinetics , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacokinetics , Catechin/administration & dosage , Catechin/pharmacokinetics , Catechin/pharmacology , Cell Line , Cell Movement/drug effects , Cell Proliferation/drug effects , Coronary Restenosis/prevention & control , Endothelial Cells/cytology , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Human Umbilical Vein Endothelial Cells , Humans , Myocytes, Smooth Muscle/cytology , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/metabolism , Receptors, Laminin/metabolism , Ribosomal ProteinsABSTRACT
The purpose of our work was to select phages displaying peptides capable of binding to vascular markers present in human atheroma, and validate their capacity to target the vascular markers in vitro and in low-density lipoprotein receptor knockout (LDLr(-/-)) mouse model of atherosclerosis. By peptide fingerprinting on human atherosclerotic tissues, we selected and isolated four different peptides sequences, which bind to atherosclerotic lesions and share significant similarity to known human proteins with prominent roles in atherosclerosis. The CTHRSSVVC-phage peptide displayed the strongest reactivity with human carotid atherosclerotic lesions (p < 0.05), when compared to tissues from normal carotid arteries. This peptide sequence shares similarity to a sequence present in the fifth scavenger receptor cysteine-rich (SRCR) domain of CD163, which appeared to bind to CD163, and subsequently, was internalized by macrophages. Moreover, the CTHRSSVVC-phage targets atherosclerotic lesions of a low-density lipoprotein receptor knockout (LDLr(-/-)) mouse model of atherosclerosis in vivo to High-Fat diet group versus Control group. Tetraazacyclododecane-1,4,7,10-tetraacetic acid-CTHRSSVVC peptide (DOTA-CTHRSSVVC) was synthesized and labeled with (111)InCl3 in >95% yield as determined by high performance liquid chromatography (HPLC), to validate the binding of the peptide in atherosclerotic plaque specimens. The results supported our hypothesis that CTHRSSVVC peptide has a remarkable sequence for the development of theranostics approaches in the treatment of atherosclerosis and other diseases.
Subject(s)
Atherosclerosis/diagnosis , Molecular Imaging/methods , Peptides/metabolism , Animals , Antigens, CD/chemistry , Antigens, Differentiation, Myelomonocytic/chemistry , Atherosclerosis/metabolism , Disease Models, Animal , Macrophages/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Peptides/chemistry , Receptors, Cell Surface/chemistry , Receptors, LDL/deficiency , Receptors, LDL/geneticsABSTRACT
Systemic delivery of therapeutic agents to solid tumors is hindered by vascular and interstitial barriers. We hypothesized that prostate tumor specific epigallocatechin-gallate (EGCg) functionalized radioactive gold nanoparticles, when delivered intratumorally (IT), would circumvent transport barriers, resulting in targeted delivery of therapeutic payloads. The results described herein support our hypothesis. We report the development of inherently therapeutic gold nanoparticles derived from the Au-198 isotope; the range of the (198)Au ß-particle (approximately 11 mm in tissue or approximately 1100 cell diameters) is sufficiently long to provide cross-fire effects of a radiation dose delivered to cells within the prostate gland and short enough to minimize the radiation dose to critical tissues near the periphery of the capsule. The formulation of biocompatible (198)AuNPs utilizes the redox chemistry of prostate tumor specific phytochemical EGCg as it converts gold salt into gold nanoparticles and also selectively binds with excellent affinity to Laminin67R receptors, which are over expressed in prostate tumor cells. Pharmacokinetic studies in PC-3 xenograft SCID mice showed approximately 72% retention of (198)AuNP-EGCg in tumors 24 h after intratumoral administration. Therapeutic studies showed 80% reduction of tumor volumes after 28 d demonstrating significant inhibition of tumor growth compared to controls. This innovative nanotechnological approach serves as a basis for designing biocompatible target specific antineoplastic agents. This novel intratumorally injectable (198)AuNP-EGCg nanotherapeutic agent may provide significant advances in oncology for use as an effective treatment for prostate and other solid tumors.
Subject(s)
Anticarcinogenic Agents/pharmacokinetics , Catechin/analogs & derivatives , Gold/pharmacokinetics , Metal Nanoparticles , Prostatic Neoplasms/drug therapy , Animals , Anticarcinogenic Agents/pharmacology , Catechin/pharmacokinetics , Catechin/pharmacology , Cell Line, Tumor , Female , Gold/pharmacology , Gold Radioisotopes/pharmacokinetics , Gold Radioisotopes/pharmacology , Humans , Male , Mice , Mice, SCID , Particle Size , Prostatic Neoplasms/pathology , Xenograft Model Antitumor Assays/methodsABSTRACT
Background: Atopic dermatitis (eczema) is an inflammatory skin condition with synthetic treatments that induce adverse effects and are ineffective. One of the proposed causes for the development of the condition is the outside-in hypothesis, which states that eczema is caused by a disruption in the skin barrier. These disruptions include developing dry cracked skin, which promotes the production of histamine. Bulbine frutescens (BF) is traditionally used to treat wounds and eczema; however, limited research has been conducted to scientifically validate this. Furthermore, gold nanoparticles (AuNPs) have been used to repair damaged skin; however, no research has been conducted on AuNPs synthesized using BF. Purpose: The study aimed to determine whether BF alleviated skin damage through wound healing, reducing the production of histamine and investigate whether AuNPs synthesized using BF would enhance biological activity. Methods: Four extracts and four synthesized AuNPs were prepared using BF and their antiproliferative and wound healing properties against human keratinocyte cells (HaCaT) were evaluated. Thereafter, the selected samples antiproliferative activity and antihistamine activity against phorbol 12-myristate 13-acetate (PMA) stimulated granulocytes were evaluated. Results: Of the eight samples, the freeze-dried leaf juice (BFE; p < 0.01) extract and its AuNPs (BFEAuNPs; p < 0.05) displayed significant wound closure at 100 µg/mL and were further evaluated. The selected samples displayed a fifty percent inhibitory concentration (IC50) of >200 µg/mL against PMA stimulated granulocytes. Compared to the untreated (media with PMA) control (0.30 ± 0.02 ng/mL), BFEAuNPs significantly inhibited histamine production at a concentration of 100 (p < 0.01) and 50 µg/mL (p < 0.001). Conclusion: BFE and BFEAuNPs stimulated wound closure, while BFEAuNPs significantly inhibited histamine production. Further investigation into BFEAuNPs in vivo wound healing activity and whether it can target histamine-associated receptors on mast cells as a potential mechanism of action should be considered.
ABSTRACT
Molecular imaging probes are a special class of pharmaceuticals that target specific biochemical signatures associated with disease and allow for noninvasive imaging on the molecular level. Because changes in biochemistry occur before diseases reach an advanced stage, molecular imaging probes make it possible to locate and stage disease, track the effectiveness of drugs, treat disease, monitor response, and select patients to allow for more personalized diagnosis and treatment of disease. Targeting agents radiolabeled with positron emitters are of interest due to their ability to quantitatively measure biodistribution and receptor expression to allow for optimal dose determinations. (68)Ga is a positron emitter, which allows for quantitative imaging through positron emission chromatography (PET). The availability of (68)Ga from a generator and its ability to form stable complexes with a variety of chelates hold promise for expanding PET utilization to facilities unable to afford their own cyclotron. Nanoparticles conjugated with various proteins and peptides derived from phage display that can be selectively targeted are being developed and evaluated for guided imaging and therapy. Herein we highlight some initial efforts in combining the enhanced selectivity of nanoparticles and peptides with (68)Ga for use as molecular imaging probes.
Subject(s)
Gallium Radioisotopes , Metal Nanoparticles , Neoplasms/diagnosis , Peptide Library , Radiopharmaceuticals , Alpha Particles , Animals , Gold , Humans , Metal Nanoparticles/therapeutic use , Neoplasms/therapyABSTRACT
Development of cancer receptor-specific gold nanoparticles will allow efficient targeting/optimum retention of engineered gold nanoparticles within tumors and thus provide synergistic advantages in oncology as it relates to molecular imaging and therapy. Bombesin (BBN) peptides have demonstrated high affinity toward gastrin-releasing peptide (GRP) receptors in vivo that are overexpressed in prostate, breast, and small-cell lung carcinoma. We have synthesized a library of GRP receptor-avid nanoplatforms by conjugating gold nanoparticles (AuNPs) with BBN peptides. Cellular interactions and binding affinities (IC(50)) of AuNP-BBN conjugates toward GRP receptors on human prostate cancer cells have been investigated in detail. In vivo studies using AuNP-BBN and its radiolabeled surrogate (198)AuNP-BBN, exhibiting high binding affinity (IC(50) in microgram ranges), provide unequivocal evidence that AuNP-BBN constructs are GRP-receptor-specific showing accumulation with high selectivity in GRP-receptor-rich pancreatic acne in normal mice and also in tumors in prostate-tumor-bearing, severe combined immunodeficient mice. The i.p. mode of delivery has been found to be efficient as AuNP-BBN conjugates showed reduced RES organ uptake with concomitant increase in uptake at tumor targets. The selective uptake of this new generation of GRP-receptor-specific AuNP-BBN peptide analogs has demonstrated realistic clinical potential in molecular imaging via x-ray computed tomography techniques as the contrast numbers in prostate tumor sites are severalfold higher as compared to the pretreatment group (Hounsfield unit = 150).
Subject(s)
Bombesin/pharmacology , Gold/pharmacology , Metal Nanoparticles/chemistry , Neoplasms/metabolism , Receptors, Bombesin/metabolism , Animals , Bombesin/administration & dosage , Bombesin/chemistry , Bombesin/pharmacokinetics , Cell Line, Tumor , Gold/administration & dosage , Gold/pharmacokinetics , Humans , Injections, Intraperitoneal , Male , Metal Nanoparticles/administration & dosage , Mice , Molecular Weight , Solubility/drug effects , Tissue Distribution/drug effects , Tomography, X-Ray Computed , Xenograft Model Antitumor AssaysABSTRACT
Purpose: We report an innovative green nanotechnology utilizing an electron-rich cocktail of phytochemicals from Yucca filamentosa L. to synthesize biocompatible gold nanoparticles without the use of any external chemical reducing agents and evaluate their anti-cancer activity. Methods: Yucca filamentosa L. extract, containing a cocktail of phytochemicals, was prepared, and used to transform gold salt into Y. filamentosa phytochemicals encapsulated gold nanoparticles (YF-AuNPs). Additionally, gum arabic stabilized YF-AuNPs (GAYF-AuNPs) were also prepared to enhance the in vitro/in vivo stability. Anticancer activity was evaluated against prostate (PC-3) and breast (MDAMB-231) cancer cell lines. Targeting abilities of gold nanoparticles were tested using pro-tumor macrophage cell lines. Results: Comprehensive characterization of new nanomedicine agents YF-AuNPs and GAYF-AuNPs revealed spherical, and monodisperse AuNPs with moderate zeta potentials (-19 and -20 mV, respectively), indicating in vitro/in vivo stability. The core size of YF-AuNPs (14 ± 5 nm) and GAYF-AuNPs (10 ± 5 nm) is suitable for optimal penetration into tumor cells through both enhanced permeability and retention (EPR) effect as well as through the receptor mediated endocytosis. Notably, YF-AuNPs exhibited potent anticancer activity against prostate (PC-3) and breast tumors (MDAMB-231) by inducing early and late apoptotic stages. Moreover, YF-AuNPs resulted in elevated levels of anti-tumor cytokines (TNF-α and IL-12) and reduced levels of pro-tumor cytokines (IL-6 and IL-10), provide compelling evidence on the immunomodulatory property of YF-AuNPs. Conclusion: Overall, these Y. filamentosa phytochemicals functionalized nano-Ayurvedic medicine agents demonstrated selective toxicity to cancer cells while sparing normal cells. Most notably, to our knowledge, this is the first study that shows YF-AuNP's targeting efficacy toward pro-tumor macrophage cell lines, suggesting an immunomodulatory pathway for cancer treatment. This work introduces a novel avenue for herbal and nano-Ayurvedic approaches to human cancer treatment, mediated through selective efficacy and immunomodulatory potential.
ABSTRACT
Lignin-containing nanocelluloses (LNCs) have the properties of both lignin and nanocellulose and could overcome the limits of both individual components in metallic nanoparticle synthesis. However, studies on LNCs are still limited, and the potential of such nanomaterials for metallic nanoparticle synthesis has not been fully unraveled. In this study, monometallic silver, gold nanoparticles, and Ag-Au-AgCl nanohybrids were synthesized in situ utilizing LNCs in a chemical-free approach. The parameters, including Ag+ and Au3+ concentrations as well as [Au3+]/[Ag+] ratios, were investigated for their effects on the nanoparticle synthesis. The characterizations, including UV-vis spectrophotometry, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), X-ray powder diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR), confirmed the coexistence of Ag, Au, and AgCl while indicating the key role of lignin and oxygen-containing functional groups in the nanoparticle synthesis. The as-synthesized AgNPs-, AuNPs-, and nanohybrids-LNC samples were tested for their antibacterial activities. In comparison to the monometallic AgNPs-LNC sample, nanohybrids-LNC synthesized with 0.063 mM Au3+ loading showed superior antibacterial activities with minimum inhibitory concentrations (MICs) at 5 µg/mL against Gram-positive Staphylococcus aureus and 10 µg/mL against Gram-negative Salmonella typhimurium with controlled Ag+ release. The results indicated that LNCs can be used to synthesize metallic nanoparticles, and the resultant Ag-Au-AgCl nanohybrids were a potent antibacterial agent with reduced environmental impacts.
ABSTRACT
TCN006, a formulation of (R)-3-Hydroxybutyrate glycerides, is a promising ingredient for enhancing ketone intake of humans. Ketones have been shown to have beneficial effects on human health. To be used by humans, TCN006 must be determined safe in appropriately designed safety studies. The results of a bacterial reverse mutation assay, an in vitro mammalian micronucleus study, and 14-and 90-day repeat dose toxicity studies in rats are reported herein. In the 14- and 90-day studies, male and female Wistar rats had free access to drinking water containing 0, 75,000, 125,000 or 200,000 ppm TCN006 for 92 and 93 days, respectively. TCN006 tested negative for genotoxicity and the no observed adverse effect level (NOAEL) for toxicity in the 14- and 90-day studies was 200,000 ppm, the highest dose administered. In the longer term study, the mean overall daily intake of TCN006 in the 200,000 ppm groups was 14,027.9 mg/kg bw/day for males and 20,507.0 mg/kg bw/day for females. At this concentration, palatability of water was likely affected, which led to a decrease in water consumption in both males and females compared to respective controls. This had no effect on the health of the animals. Although the rats were administered very high levels of (R)-3-Hydroxybutyrate glycerides, there were no signs of ketoacidosis.
Subject(s)
Drinking Water , Glycerides , Humans , Rats , Male , Female , Animals , Rats, Wistar , 3-Hydroxybutyric Acid , Body Weight , MammalsABSTRACT
Melanoma cells secrete pro-angiogenic factors, which stimulates growth, proliferation and metastasis, and therefore are key therapeutic targets. Buddleja saligna (BS), and an isolated triterpenoid mixture (DT-BS-01) showed a fifty percent inhibitory concentration (IC50) of 33.80 ± 1.02 and 5.45 ± 0.19 µg/mL, respectively, against melanoma cells (UCT-MEL-1) with selectivity index (SI) values of 1.64 and 5.06 compared to keratinocytes (HaCat). Cyclooxygenase-2 (COX-2) inhibition was observed with IC50 values of 35.06 ± 2.96 (BS) and 26.40 ± 4.19 µg/mL (DT-BS-01). BS (30 µg/mL) significantly inhibited interleukin (IL)-6 (83.26 ± 17.60%) and IL-8 (100 ± 0.2%) production, whereas DT-BS-01 (5 µg/mL) showed 51.07 ± 2.83 (IL-6) and 0 ± 6.7% (IL-8) inhibition. Significant vascular endothelial growth factor (VEGF) inhibition, by 15.84 ± 4.54 and 12.21 ± 3.48%, respectively, was observed. In the ex ovo chick embryo yolk sac membrane assay (YSM), BS (15 µg/egg) significantly reduced new blood vessel formation, with 53.34 ± 11.64% newly formed vessels. Silver and palladium BS nanoparticles displayed noteworthy SI values. This is the first report on the significant anti-angiogenic activity of BS and DT-BS-01 and should be considered for preclinical trials as there are currently no US Food and Drug Administration (FDA) approved drugs to inhibit angiogenesis in melanoma.
ABSTRACT
Gold nanoparticles from plant extracts and their bioactive compounds to treat various maladies have become an area of interest to many researchers. Acne vulgaris is an inflammatory disease of the pilosebaceous unit caused by the opportunistic bacteria Cutibacterium acnes and Staphylococcus epidermis. These bacteria are not only associated with inflammatory acne but also with prosthetic-implant-associated infections and wounds. Studies have hypothesised that these bacteria have a mutualistic relationship and act as a multispecies system. It is believed that these bacteria form a multispecies biofilm under various conditions and that these biofilms contribute to increased antibiotic resistance compared to single-species biofilms. This study aimed to investigate the antibacterial and wound healing potential of synthesised gold nanoparticles (AuNPs) from an endemic South African plant, Plectranthus aliciae (AuNPPAE), its major compound rosmarinic acid (AuNPRA) and a widely used antibiotic, tetracycline (AuNPTET). Synthesised gold nanoparticles were successfully formed and characterised using ultraviolet-visible spectroscopy (UV-vis), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), zeta potential (ζ-potential), high-resolution transmission electron microscopy (HRTEM), and selected area electron diffraction (SAED), and they were investigated for stability under various biological conditions. Stable nanoparticles were formed with ζ-potentials of -18.07 ± 0.95 mV (AuNPPAE), -21.5 ± 2.66 mV (AuNPRA), and -39.83 ± 1.6 mV (AuNPTET). The average diameter of the AuNPs was 71.26 ± 0.44 nm, 29.88 ± 3.30 nm, and 132.6 ± 99.5 nm for AuNPPAE, AuNPRA, and AuNPTET, respectively. In vitro, biological studies confirmed that although no antibacterial activity or biofilm inhibition was observed for the nanoparticles tested on the multispecies C. acnes and S. epidermis systems, these samples had potential wound closure activity. Gold nanoparticles formed with rosmarinic acid significantly increased wound closure by 21.4% at 25% v/v (≈29.2 µg/mL) compared to the negative cell control and the rosmarinic acid compound at the highest concentration tested of 500 µg/mL. This study concluded that green synthesised gold nanoparticles of rosmarinic acid could potentially be used for treating wounds.
ABSTRACT
The rapidly growing interest in the application of nanoscience in the future design of radiopharmaceuticals and the development of nanosized radiopharmaceuticals in the late 2000's, resulted in the creation of a Coordinated Research Project (CRP) by the International Atomic Energy Agency (IAEA) in 2014. This CRP entitled 'Nanosized delivery systems for radiopharmaceuticals' involved a team of expert scientist from various member states. This team of scientists worked on a number of cutting-edge areas of nanoscience with a focus on developing well-defined, highly effective and site-specific delivery systems of radiopharmaceuticals. Specifically, focus areas of various teams of scientists comprised of the development of nanoparticles (NPs) based on metals, polymers, and gels, and their conjugation/encapsulation or decoration with various tumor avid ligands such as peptides, folates, and small molecule phytochemicals. The research and development efforts also comprised of developing optimum radiolabeling methods of various nano vectors using diagnostic and therapeutic radionuclides including Tc-99m, Ga-68, Lu-177 and Au-198. Concerted efforts of teams of scientists within this CRP has resulted in the development of various protocols and guidelines on delivery systems of nanoradiopharmaceuticals, training of numerous graduate students/post-doctoral fellows and publications in peer reviewed journals while establishing numerous productive scientific networks in various participating member states. Some of the innovative nanoconstructs were chosen for further preclinical applications-all aimed at ultimate clinical translation for treating human cancer patients. This review article summarizes outcomes of this major international scientific endeavor.
ABSTRACT
PURPOSE: The purpose of the present study was to explore the utilization of cinnamon-coated gold nanoparticles (Cin-AuNPs) as CT/optical contrast-enhancement agents for detection of cancer cells. METHODS: Cin-AuNPs were synthesized by a "green" procedure, and the detailed characterization was performed by physico-chemical analysis. Cytotoxicity and cellular uptake studies were carried out in normal human fibroblast and cancerous (PC-3 and MCF-7) cells, respectively. The efficacy of detecting cancerous cells was monitored using a photoacoustic technique. In vivo biodistribution was studied after IV injection of Cin-AuNPs in mice, and also a CT phantom model was generated. RESULTS: Biocompatible Cin-AuNPs were synthesized with high purity. Significant uptake of these gold nanoparticles was observed in PC-3 and MCF-7 cells. Cin-AuNPs internalized in cancerous cells facilitated detectable photoacoustic signals. In vivo biodistribution in normal mice showed steady accumulation of gold nanoparticles in lungs and rapid clearance from blood. Quantitative analysis of CT values in phantom model revealed that the cinnamon-phytochemical-coated AuNPs have reasonable attenuation efficiency. CONCLUSIONS: The results indicate that these non-toxic Cin-AuNPs can serve as excellent CT/ photoacoustic contrast-enhancement agents and may provide a novel approach toward tumor detection through nanopharmaceuticals.
Subject(s)
Gold/chemistry , Metal Nanoparticles/chemistry , Nanotechnology/methods , Neoplasms/diagnosis , Radiographic Image Enhancement/methods , Animals , Cell Line, Tumor , Cinnamomum zeylanicum/chemistry , Contrast Media/chemistry , Fibroblasts , Humans , Mice , Neoplasms/pathology , Phantoms, Imaging , Signal Processing, Computer-Assisted , Tissue DistributionABSTRACT
BACKGROUND AND OBJECTIVES: We tagged melanoma cells with gold nanoparticles to show their viability for increasing sensitivity in a photoacoustic detection system. Ultimately, this study models the detection of circulating tumor cells, which are an important prognostic factor in the progress of melanoma. STUDY DESIGN/MATERIALS AND METHODS: A Q-switched, tunable Nd:YAG laser was used to irradiate cells in both a stationary and flow set-up. Photoacoustic signals were measured using a polyvinylidene fluoride (PVDF) film in the stationary test, and a commercially available ultrasonic probe for flow tests. Both unmodified melanoma cells and gold nanoparticle (AuNP) tagged melanoma were tested. RESULTS: AuNP tagged melanoma in a stationary set-up showed an average of 0.227 mV/mJ larger signal than the untagged, indicating a signal increase of 34%. At 500 nm there is a maximum difference of 0.295 mV/mJ, or a 41% increase. In flow tests, the ultrasound probe was able to detect single cells, but the increased signal from AuNP tagging was minimal. CONCLUSION: AuNP tagging proved to give an increased photoacoustic signal allowing greater sensitivity in stationary metastasized melanoma detection systems using photoacoustics.
Subject(s)
Acoustics/instrumentation , Biomarkers, Tumor/analysis , Gold/analysis , Melanoma/chemistry , Metal Nanoparticles/analysis , Neoplastic Cells, Circulating/chemistry , Skin Neoplasms/chemistry , Cell Line, Tumor , Cell Separation/methods , Flow Cytometry/methods , Humans , Lasers, Semiconductor , Melanoma/pathology , Molecular Probe Techniques , Neoplastic Cells, Circulating/pathology , Pattern Recognition, Automated , Skin Neoplasms/pathologyABSTRACT
Gold-thioguanine nanoconjugates (AuNP-TG) of size 3-4 nm were synthesized and the ratio between gold and 6-Thioguanine (TG) was estimated as ~1:1.5 using a cyanide digestion method and confirmed by flame atomic absorption spectroscopic analysis. AuNP-TG constructs showed high in vitro stability under different pH conditions and biologically relevant solutions for a period of 24 hours. Reaction of AuNP-TG with europium or platinum salts resulted in the formation of organized self-assembled metallo-networks.
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The application of nanotechnology in nuclear medicine offers attractive therapeutic opportunities for the treatment of various diseases, including cancer. Indeed, nanoparticles-conjugated targeted alpha-particle therapy (TAT) would be ideal for localized cell killing due to high linear energy transfer and short ranges of alpha emitters. New approaches in radiolabeling are necessary because chemical radiolabeling techniques are rendered sub-optimal due to the presence of recoil energy generated by alpha decay, which causes chemical bonds to break. This review attempts to cover, in a concise fashion, various aspects of physics, radiobiology, and production of alpha emitters, as well as highlight the main problems they present, with possible new approaches to mitigate those problems. Special emphasis is placed on the strategies proposed for managing recoil energy. We will also provide an account of the recent studies in vitro and in vivo preclinical investigations of α-particle therapy delivered by various nanosystems from different materials, including inorganic nanoparticles, liposomes, and polymersomes, and some carbon-based systems are also summarized.
ABSTRACT
Green nanotechnology has drawn major attention because of its ecofriendly and economical biosynthetic protocols. Synthesis of gold nanoparticles (AuNPs) using plant secondary metabolites is considered as a safer and cheaper option. Plants contain phytochemicals that has been used traditionally for treatment of various diseases, and proved to be non-toxic to healthy tissues. These phytochemicals play an important role in bio-reduction processes as reducing and stabilizing agents, and renders NPs selective toxicity towards diseased tissues. The study reports on the synthesis of AuNPs using Acai berry (AB) and Elderberry (EB) extracts and their anti-cancer properties. Formation of berry-AuNPs was confirmed through measurement of physico-chemical properties. The stability of the AuNPs was tested in biocompatible solutions. Anti-cancer activity of berry extracts and AuNPs was evaluated on the prostate (PC-3) and pancreatic (Panc-1) cancer cells. The berry extracts did not show toxicity to the cells, except for AB extracts on PC-3 cells at higher concentrations. The berry-AuNPs showed potential anti-cancer activities, and these effects could be further exploited for treatment of both the prostate and pancreatic cancers. Further studies are required to study the NP mechanism of action and specificity, as well as identify the phytochemicals involved in the synthesis of AuNPs.
ABSTRACT
PURPOSE: We report herein bombesin peptide conjugated water-soluble chitosan gallate as a template for rapid one-pot synthesis of gold nanoparticles (AuNPs) with capabilities to target receptors on prostate cancer cells. METHODS: Water-soluble chitosan (WCS), anchored with gallic acid (GA) and LyslLys3 (1,4,7,10-tetraazacyclo dodecane-1,4,7,10-tetraacetic acid) bombesin 1-14 (DBBN) peptide, provides a tumor targeting nanomedicine agent. WCS nanoplatforms provide attractive strategies with built-in capabilities to reduce gold (III) to gold nanoparticles with stabilizing and tumor-targeting capabilities. WCS-GA-DBBN encapsulation around gold nanoparticles affords optimum in vitro stability. RESULTS: The DBBN content in the WCS-GA-DBBN sample was ~27%w/w. The antioxidant activities of WCS-GA and WCS-GA-DBBN nanocolloids were enhanced by 12 times as compared to the nascent WCS. AuNPs with a desirable hydrodynamic diameter range of 40-60 nm have been efficiently synthesized using WCS-GA and WCS-GA-DBBN platforms. The AuNPs were stable over 4 days after preparation and ~3 days after subjecting to all relevant biological fluids. The AuNPs capped with WCS-GA-DBBN peptide exhibited superior cellular internalization into prostate tumor (PC-3) cells with evidence of receptor mediated endocytosis. CONCLUSION: The AuNPs capped with WCS-GA-DBBN exhibited selective affinity toward prostate cancer cells. AuNPs conjugated with WCS-GA-DBBN serve as a new generation of theranostic agents for treating various neoplastic diseases, thus opening-up new applications in oncology.
Subject(s)
Chitosan , Metal Nanoparticles , Prostatic Neoplasms , Bombesin , Cell Line, Tumor , Chitosan/analogs & derivatives , Gold , Humans , Male , Peptides , Prostatic Neoplasms/drug therapy , WaterABSTRACT
INTRODUCTION: Functionalization of water-soluble chitosan (WSCS) nanocolloids with, gold nanoparticles (AuNPs), and LyslLys3 (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-bombesin 1-14 (DOTA-BBN) peptide affords an innovative pathway to produce prostate tumor cell-specific nanomedicine agents with potential applications in molecular imaging and therapy. METHODS: The preparation involves the production and full characterization of water-soluble chitosan (WSCS), via gamma (γ) rays (80 kGy) irradiation, followed by DOTA-BBN conjugation for subsequent use as an effective template toward the synthesis of tumor cell-specific AuNPs-WSCS-DOTA-BBN. RESULTS: The WSCS-DOTA-BBN polymeric nanoparticles (86 ± 2.03 nm) served multiple roles as reducing and stabilizing agents in the overall template synthesis of tumor cell-targeted AuNPs. The AuNPs capped with WSCS and WSCS-DOTA-BBN exhibited average Au-core diameter of 17 ± 8 nm and 20 ± 7 nm with hydrodynamic diameters of 56 ± 1 and 67± 2 nm, respectively. The AuNPs-WSCS-DOTA-BBN showed optimum in vitro stability in biologically relevant solutions. The targeted AuNPs showed selective affinity toward GRP receptors overexpressed in prostate cancer cells (PC-3 and LNCaP). DISCUSSION: The AuNPs-WSCS-DOTA-BBN displayed cytotoxicity effects against PC-3 and LNCaP cancer cells, with concomitant safety toward the HAECs normal cells. The AuNPs-WSCS-DOTA-BBN showed synergistic targeting toward tumor cells with selective cytotoxicity of AuNPs towards PC-3 and LNCaP cells. Our investigations provide compelling evidence that AuNPs functionalized with WSCS-DOTA-BBN is an innovative nanomedicine approach for use in molecular imaging and therapy of GRP receptor-positive tumors. The template synthesis of AuNPs-WSCS-DOTA-BBN serves as an excellent non-radioactive surrogate for the development of the corresponding 198AuNPs theragnostic nanoradiopharmaceutical for use in cancer diagnosis and therapy.