Radiosensitization of Prostate Cancers In Vitro and In Vivo to Erbium-filtered Orthovoltage X-rays Using Actively Targeted Gold Nanoparticles

Abstract : Gold nanoparticles (GNPs) have diverse optical and photo-thermal properties. It is used for diagnostic imaging because of their ability to absorb near infrared (NIR) and X-rays, and their surface enhanced Raman scattering properties. Recently they are used for drug delivery and more particularly photothermal treatment. Their ability to absorb NIR energy and convert it to heat by a Surface Plasmon Resonance mechanism has made these materials promising for the treatment of tumors. GNPs having diameter higher than 1.4–1.5 nm is found nontoxic to the environment. In the present work, polymer anchored GNPs are synthesized by reducing AuIII to Au0 in presence of either chitosan or polyvinyl alcohol, which act as in situ reducers cum stabilizers. Microscopic techniques (TEM, SEM and DLS) are used to analyse the size, surface morphology and size distribution respectively. The unique mucoadhesive properties of chitosan particularly make the system promising with respect to antimicrobial (anti-bacteria as well as anti-fungus) activities. An attempt has been made to understand the mechanistic path involved in antimicrobial activities. Antimicrobial potential of chitosan anchored gold nanoparticles (GNPc) are noticed even at very low dose. The results of bio-chemical analysis (MDA, NBT, DNA fragmentation and over-expression of heat shock protein) clearly explain antimicrobial activities. Additionally, gold chitosan systems interact with microbial DNA and inhibit the action of DNA repair enzyme. Interestingly, in vitro (rat peritoneal MФ) or in vivo (Wistar rat) analysis exhibits negligible cytotoxicy. Thus the synthesized material (particularly GNPc) is promising as an effective nano therapeutic agent.

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Dosimetry and Radioenhancement Comparison of Gold Nanoparticles in Kilovoltage and Megavoltage Radiotherapy using MAGAT Polymer Gel Dosimeter

Journal of Biomedical Physics and Engineering ◽

10.31661/jbpe.v9i2apr.827 ◽

2019 ◽

Vol 9 (2Apr) ◽

Cited By ~ 1

Author(s):

S Farahani ◽

N Riyahi Alam ◽

S Haghgoo ◽

M Khoobi ◽

Gh Geraily ◽

...

Keyword(s):

Gold Nanoparticles ◽

3D Visualization ◽

Energy Levels ◽

Polymer Gel ◽

External Radiotherapy ◽

Dose Enhancement ◽

Internal Radiotherapy ◽

Boost Radiotherapy

Background: Numerous unique characteristics of the nanosized gold, including high atomic number, low toxicity, and high biocompatibility make it one of the most appropriate nanostructures to boost radiotherapy efficacy. Many in-vivo and in-vitro investigations have indicated that gold nanoparticles (AuNPs) can significantly increase tumor injuries in low kilovoltage radiotherapy. While deep-lying tumors require much higher energy levels with greater penetration power, and investigations carried out in megavoltage energy range show contradictory results.Objective: In this study, we quantitatively assess and compare dose enhancement factors (DEFs) obtained through AuNPs under radiation of Cobalt-60 source (1.25MeV) versus Iridium-192 source (0.380 KeV) using MAGAT gel dosimeter.Material and Methods: MAGAT polymer gel in both pure and combined with 0.2 mM AuNPs was synthesized. In order to quantify the effect of energy on DEF, irradiation was carried out by Co-60 external radiotherapy and Ir-192 internal radiotherapy. Finally, readings of irradiated and non-irradiated gels were performed by MR imaging.Result: The radiation-induced R2 (1/T2) changes of the gel tubes doped with AuNPs compared to control samples, upon irradiation of beams released by Ir-192 source showed a significant dose enhancement (15.31% ±0.30) relative to the Co-60 external radiotherapy (5.85% ±0.14).Conclusion: This preliminary study suggests the feasibility of using AuNPs in radiation therapy (RT), especially in low-energy sources of brachytherapy. In addition, MAGAT polymer gel, as a powerful dosimeter, could be used for 3D visualization of radiation dose distribution of AuNPs in radiotherapy.

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Cruciferous Vegetables as Antioxidative, Chemopreventive and Antineoplasic Functional Foods: Preclinical and Clinical Evidences of Sulforaphane Against Prostate Cancers

Current Pharmaceutical Design ◽

10.2174/1381612825666190116124233 ◽

2019 ◽

Vol 24 (40) ◽

pp. 4779-4793 ◽

Cited By ~ 4

Author(s):

Paulo M.P. Ferreira ◽

Lays A.R.L. Rodrigues ◽

Lunna Paula de Alencar Carnib ◽

Paulo Víctor de Lima Sousa ◽

Luis Michel Nolasco Lugo ◽

...

Keyword(s):

Histone Deacetylases ◽

Cruciferous Vegetables ◽

Tumor Cell Death ◽

Antitumor Effects ◽

Antiapoptotic Proteins ◽

Cycle Arrest ◽

Government Documents ◽

Prostate Cancers

Background: Sulforaphane (SF, 1-isothiocyanato-4-(methyl-sulfinyl)-butane) is found in broccoli, cabbage and cauliflower. Methods: we performed a critical review on the antioxidative, chemopreventive and antitumor effects of SF from cruciferous vegetables against prostate cancers and molecular pathways. For a complete and reliable review, primary and secondary resources were used, including original and review articles, books and government documents published until March 2018. Articles that are in duplicity and disconnected are not considered for review. SF is derived from glucoraphanin (4-methyl-sulfinyl-butyl-glucosinate), being one of the most commonly found isothiocyanates in vegetables from Brassica spp., especially in broccoli samples. In vitro studies indicate that SF induces apoptosis in a dependent or non-dependent method of androgens by transcription of tumor suppressor genes, oxidation response and higher expression of phase II enzymes in prostate cancer cells. Sulforaphane also decreases transcription of the nuclear factor kB and antiapoptotic proteins, expression of cyclin D2 and survivin and DNA synthesis, increases Nrf2 gene activity, interferes with genome compacting by inhibition of histone deacetylases and disrupts Hsp90 complexes, which cause cell cycle arrest, mitosis interruption, activation of caspases and mitochondria depolarization. Conclusion: SF and cruciferous vegetables play antioxidative and chemopreventive role, delaying or blocking in vivo carcinogenesis, causing biochemical and epigenetic changes, preventing, delaying, or reversing preneoplastic or advanced prostate lesions, and frequently activating tumor cell death by intrinsic methods of apoptosis. These outcomes encourage the consumption of Brassica specimens, which could be easily achieved by the incorporation of food and vegetables rich in cruciferous isothiocyanates in the diet.

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Optimization of X-ray Investigations in Dentistry Using Optical Coherence Tomography

Sensors ◽

10.3390/s21134554 ◽

2021 ◽

Vol 21 (13) ◽

pp. 4554

Author(s):

Ralph-Alexandru Erdelyi ◽

Virgil-Florin Duma ◽

Cosmin Sinescu ◽

George Mihai Dobre ◽

Adrian Bradu ◽

...

Keyword(s):

Optical Coherence Tomography ◽

Radiation Dose ◽

Imaging Techniques ◽

Image Resolution ◽

Optical Coherence ◽

X Rays ◽

High Quality ◽

X Ray

The most common imaging technique for dental diagnoses and treatment monitoring is X-ray imaging, which evolved from the first intraoral radiographs to high-quality three-dimensional (3D) Cone Beam Computed Tomography (CBCT). Other imaging techniques have shown potential, such as Optical Coherence Tomography (OCT). We have recently reported on the boundaries of these two types of techniques, regarding. the dental fields where each one is more appropriate or where they should be both used. The aim of the present study is to explore the unique capabilities of the OCT technique to optimize X-ray units imaging (i.e., in terms of image resolution, radiation dose, or contrast). Two types of commercially available and widely used X-ray units are considered. To adjust their parameters, a protocol is developed to employ OCT images of dental conditions that are documented on high (i.e., less than 10 μm) resolution OCT images (both B-scans/cross sections and 3D reconstructions) but are hardly identified on the 200 to 75 μm resolution panoramic or CBCT radiographs. The optimized calibration of the X-ray unit includes choosing appropriate values for the anode voltage and current intensity of the X-ray tube, as well as the patient’s positioning, in order to reach the highest possible X-rays resolution at a radiation dose that is safe for the patient. The optimization protocol is developed in vitro on OCT images of extracted teeth and is further applied in vivo for each type of dental investigation. Optimized radiographic results are compared with un-optimized previously performed radiographs. Also, we show that OCT can permit a rigorous comparison between two (types of) X-ray units. In conclusion, high-quality dental images are possible using low radiation doses if an optimized protocol, developed using OCT, is applied for each type of dental investigation. Also, there are situations when the X-ray technology has drawbacks for dental diagnosis or treatment assessment. In such situations, OCT proves capable to provide qualitative images.

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Biocompatibility of gold nanoparticles: In-vitro and In-vivo study

Materials Today Proceedings ◽

10.1016/j.matpr.2020.12.826 ◽

2021 ◽

Vol 42 ◽

pp. 3041-3045

Author(s):

Rua J. Kadhim ◽

Esraa H. Karsh ◽

Zainab J. Taqi ◽

Majid S. Jabir

Keyword(s):

Gold Nanoparticles ◽

In Vivo Study

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In vitro and in vivo applications of Euphorbia wallichii shoot extract-mediated gold nanospheres

Green Processing and Synthesis ◽

10.1515/gps-2021-0013 ◽

2021 ◽

Vol 10 (1) ◽

pp. 101-111

Author(s):

Rehman Ullah ◽

Sumaira Shah ◽

Zahir Muhammad ◽

Sajjad Ali Shah ◽

Shah Faisal ◽

...

Keyword(s):

Gold Nanoparticles ◽

Muscular Contraction ◽

Surface Plasmon Resonance Peak ◽

Plasmon Resonance Peak ◽

Optical Absorption Peak ◽

Visible Spectra ◽

Scattering Spectra ◽

Dose Dependent

Abstract The current study was designed to investigate the potential of Euphorbia wallichii shoot extract for reducting Au3+ and stabilizing gold nanoparticles. UV-visible spectra of gold nanoparticles showed obvious surface plasmon resonance peak at 548 nm. Microscopy (SEM and TEM) showed spherical dimensions, and the energy dispersive X-ray spectra displayed the strongest optical absorption peak for gold (Au) at 2.1 keV. Dynamic light scattering spectra represent polydispersed mixture with particulate diameter of 2.5–103.2 nm. The IR spectra confirm the potential functional groups of shoot extract responsible for the reduction of Au3+ to gold nanoparticles which exhibit tremendous antibacterial potential of 76.31%, 68.47%, 79.85%, 48.10%, and 65.53% against Escherichia coli, Staphylococcus aureus, Bacillus pumilus, Pseudomonas aeruginosa, and Klebsiella pneumoniae, respectively. Gold nanoparticles showed markedly elevated fungicidal potency compared to the shoot extract alone against the tested fungal strains. IC50 for 2,2-diphenyl-1-picrylhydrazyl scavenging was 31.52, 18.29, and 15.32 µg/mL at 30, 60, and 90 min of reaction time, respectively. Both shoot extract and nanoparticles revealed 71% mortality at 100 µg/mL, with LD90 values of 310.56 µg/mL. Experimental mice acquired dose-dependent analgesia of 54.21%, 82.60%, and 86.53% when treated with gold nanoparticles at 50, 100, and 200 mg/kg bw. Inhibition of gastrointestinal muscular contraction was 21.16%, 30.49%, and 40.19% in mice feed with 50, 100, and 200 mg/kg bw, respectively.

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Surface-Initiated Atom Transfer Polymerized Anionic Corona on Gold Nanoparticles for Anti-Cancer Therapy

Pharmaceutics ◽

10.3390/pharmaceutics12030261 ◽

2020 ◽

Vol 12 (3) ◽

pp. 261

Author(s):

Wei Mao ◽

Sol Lee ◽

Ji Un Shin ◽

Hyuk Sang Yoo

Keyword(s):

Gold Nanoparticles ◽

Transfection Efficiency ◽

Cancer Therapeutics ◽

Atom Transfer ◽

Layer By Layer ◽

Dependent Manner ◽

Metallic Particles ◽

Anti Cancer

Surface initiated atom transfer radical polymerization (SI-ATRP) documented a simple but efficient technique to grow a dense polymer layer on any surface. Gold nanoparticles (AuNPs) give a broad surface to immobilize sulfhyryl group-containing initiators for SI-ATRP; in addition, AuNPs are the major nanoparticulate carriers for delivery of anti-cancer therapeutics, since they are biocompatible and bioinert. In this work, AuNPs with a disulfide initiator were polymerized with sulfoethyl methacrylate by SI-ATRP to decorate the particles with anionic corona, and branched polyethyeleneimine (PEI) and siRNA were sequentially layered onto the anionic corona of AuNP by electrostatic interaction. The in vitro anti-cancer effect confirmed that AuNP with anionic corona showed higher degrees of apoptosis as well as suppression of the oncogene expression in a siRNA dose-dependent manner. The in vivo study of tumor-bearing nude mice revealed that mice treated with c-Myc siRNA-incorporated AuNPs showed dramatically decreased tumor size in comparison to those with free siRNA for 4 weeks. Furthermore, histological examination and gene expression study revealed that the decorated AuNP significantly suppressed c-Myc expression. Thus, we envision that the layer-by-layer assembly on the anionic brushes can be potentially used to incorporate nucleic acids onto metallic particles with high transfection efficiency.

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Evaluation of the in vitro and in vivo proinflammatory activities of gold (+) and gold (−) nanoparticles

Inflammation Research ◽

10.1007/s00011-017-1078-7 ◽

2017 ◽

Vol 66 (11) ◽

pp. 981-992 ◽

Cited By ~ 7

Author(s):

Isabelle Durocher ◽

Claudie Noël ◽

Valérie Lavastre ◽

Denis Girard

Keyword(s):

Gold Nanoparticles

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Antitumor Activity and Mechanism of Action of the Hormonotoxin, an LHRH Analog Conjugated to Dermaseptin-B2, a Multifunctional Antimicrobial Peptide

10.21203/rs.3.rs-757762/v1 ◽

2021 ◽

Author(s):

Mickael COUTY ◽

Marie DUSAUD ◽

Mickael MIRO-PADOVANI ◽

Liuhui ZHANG ◽

Patricia ZADIGUE ◽

...

Keyword(s):

Antitumor Activity ◽

Antimicrobial Peptide ◽

Tumor Cell Line ◽

Experimental Approaches ◽

Prostate Cancers ◽

Innovative Drugs ◽

Therapeutic Alternatives ◽

Prostate Tumor Cells

Abstract Prostate cancer represents the most common cancer in men. For patients with advanced or metastatic form, treatments will be able to slow down the progression but cannot cure it even with the used of new targeted therapies. In this context, the development of innovative drugs resulting from the exploration of biodiversity could open new therapeutic alternatives. Dermaseptin-B2 (DRS-B2), a natural multifunctional antimicrobial peptide isolated from the Amazonian frog skin, has been reported to possess antitumor and antiangiogenic activities. To improve DRS-B2 pharmacological properties and target prostate tumor cells more specifically, we have developed a chimeric molecule, called Hormonotoxin (H-B2) which is composed of a DRS-B2 combined with a hormonal analog, d-Lys6-LHRH, to target LHRH-Receptor which is overexpressed in more than 85% of prostate cancers. In vitro H-B2 has a significant antiproliferative effect on the PC3 tumor cell line, with an IC50 value close to that of DRS-B2. The antitumor activity of H-B2 was confirmed in vivo in mouse model xenografted with PC3 tumors and appears to be better tolerated than DRS-B2. Biophysical experiments showed that the addition of the hormonal analog to DRS-B2 did not alter either its secondary structure or its biological activity. Combination of different experimental approaches indicated that H-B2 induces cell death by an apoptotic mechanism whereas DRS-B2 was shown to induce it by necrosis. These results could explain the H-B2 less toxicity compared to DRS-B2. H-B2 represents a promising targeting approach for cancer therapy.

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Exposure to airborne gold nanoparticles: a review of current toxicological data on the respiratory tract

Journal of Nanoparticle Research ◽

10.1007/s11051-020-04966-9 ◽

2020 ◽

Vol 22 (8) ◽

Author(s):

Barbara De Berardis ◽

Magda Marchetti ◽

Anna Risuglia ◽

Federica Ietto ◽

Carla Fanizza ◽

...

Keyword(s):

Gold Nanoparticles ◽

Human Health ◽

Large Scale ◽

Current Knowledge ◽

Engineered Nanoparticles ◽

In Vivo Studies ◽

Field Exposure ◽

The Impact

AbstractIn recent years, the introduction of innovative low-cost and large-scale processes for the synthesis of engineered nanoparticles with at least one dimension less than 100 nm has led to countless useful and extensive applications. In this context, gold nanoparticles stimulated a growing interest, due to their peculiar characteristics such as ease of synthesis, chemical stability and optical properties. This stirred the development of numerous applications especially in the biomedical field. Exposure of manufacturers and consumers to industrial products containing nanoparticles poses a potential risk to human health and the environment. Despite this, the precise mechanisms of nanomaterial toxicity have not yet been fully elucidated. It is well known that the three main routes of exposure to nanomaterials are by inhalation, ingestion and through the skin, with inhalation being the most common route of exposure to NPs in the workplace. To provide a complete picture of the impact of inhaled gold nanoparticles on human health, in this article, we review the current knowledge about the physico-chemical characteristics of this nanomaterial, in the size range of 1–100 nm, and its toxicity for pulmonary structures both in vitro and in vivo. Studies comparing the toxic effect of NPs larger than 100 nm (up to 250 nm) are also discussed.

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