scholarly journals In Vitro and In Vivo Genotoxicity Analysis of Gold Nanoparticles

2021 ◽  
Vol 11 (3) ◽  
pp. 3826-3833

Gold nanoparticles have been well recognized for biomedical applications, especially cancer therapeutics. As a preliminary step, it is necessary to investigate the genotoxicity of gold nanoparticles under in vitro and in vivo conditions. In vitro, chromosomal aberration study results showed that gold nanoparticles of 5 mg/ml concentration did not increase the percentage of chromosomal aberration in human peripheral blood lymphocyte cells compared to the negative control. Gold nanoparticles were evaluated erythrocyte micronucleus formation by in vivo micronucleus assay, and results showed no apparent micronucleus formation in mice after 42h exposure of gold nanoparticles. Gold nanoparticles of 600 mg/kg (body weight) were non-clastogenic in swiss albino mice.

Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 261
Author(s):  
Wei Mao ◽  
Sol Lee ◽  
Ji Un Shin ◽  
Hyuk Sang Yoo

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.


Molecules ◽  
2020 ◽  
Vol 25 (15) ◽  
pp. 3489
Author(s):  
Daniela Ferreira ◽  
David Fontinha ◽  
Catarina Martins ◽  
David Pires ◽  
Alexandra R. Fernandes ◽  
...  

Cancer remains a complex medical challenge and one of the leading causes of death worldwide. Nanomedicines have been proposed as innovative platforms to tackle these complex diseases, where the combination of several treatment strategies might enhance therapy success. Among these nanomedicines, nanoparticle mediated delivery of nucleic acids has been put forward as key instrument to modulate gene expression, be it targeted gene silencing, interference RNA mechanisms and/or gene edition. These novel delivery systems have strongly relied on nanoparticles and, in particular, gold nanoparticles (AuNPs) have paved the way for efficient delivery systems due to the possibility to fine-tune their size, shape and surface properties, coupled to the ease of functionalization with different biomolecules. Herein, we shall address the different molecular tools for modulation of expression of oncogenes and tumor suppressor genes and discuss the state-of-the-art of AuNP functionalization for nucleic acid delivery both in vitro and in vivo models. Furthermore, we shall highlight the clinical applications of these spherical AuNP based conjugates for gene delivery, current challenges, and future perspectives in nanomedicine.


2019 ◽  
Vol 98 (9) ◽  
pp. 350-355

Introduction: There is evidence that mesenchymal stem cells (MSCs) could trans-differentiate into the liver cells in vitro and in vivo and thus may be used as an unfailing source for stem cell therapy of liver disease. Combination of MSCs (with or without their differentiation in vitro) and minimally invasive procedures as laparoscopy or Natural Orifice Transluminal Endoscopic Surgery (NOTES) represents a chance for many patients waiting for liver transplantation in vain. Methods: Over 30 millions of autologous MSCs at passage 3 were transplanted via the portal vein in an eight months old miniature pig. The deposition of transplanted cells in liver parenchyma was evaluated histologically and the trans-differential potential of CM-DiI labeled cells was assessed by expression of pig albumin using immunofluorescence. Results: Three weeks after transplantation we detected the labeled cells (solitary, small clusters) in all 10 samples (2 samples from each lobe) but no diffuse distribution in the samples. The localization of CM-DiI+ cells was predominantly observed around the portal triads. We also detected the localization of albumin signal in CM-DiI labeled cells. Conclusion: The study results showed that the autologous MSCs (without additional hepatic differentiation in vitro) transplantation through the portal vein led to successful infiltration of intact miniature pig liver parenchyma with detectable in vivo trans-differentiation. NOTES as well as other newly developed surgical approaches in combination with cell therapy seem to be very promising for the treatment of hepatic diseases in near future.


Author(s):  
S Farahani ◽  
N Riyahi Alam ◽  
S Haghgoo ◽  
M Khoobi ◽  
Gh Geraily ◽  
...  

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.


2020 ◽  
Vol 15 (1) ◽  
pp. 2-13 ◽  
Author(s):  
Hongyu Tao ◽  
Ling Zuo ◽  
Huanli Xu ◽  
Cong Li ◽  
Gan Qiao ◽  
...  

Background: In recent years, many novel alkaloids with anticancer activity have been found in China, and some of them are promising for developing as anticancer agents. Objective: This review aims to provide a comprehensive overview of the information about alkaloid anticancer agents disclosed in Chinese patents, and discusses their potential to be developed as anticancer drugs used clinically. Methods: Anticancer alkaloids disclosed in Chinese patents in recent 5 years were presented according to their mode of actions. Their study results published on PubMed, and SciDirect databases were presented. Results: More than one hundred anticancer alkaloids were disclosed in Chinese patents and their mode of action referred to arresting cell cycle, inhibiting protein kinases, affecting DNA synthesis and p53 expression, etc. Conclusion: Many newly found alkaloids displayed potent anticancer activity both in vitro and in vivo, and some of the anticancer alkaloids acted as protein kinase inhibitors or CDK inhibitors possess the potential for developing as novel anticancer agents.


2019 ◽  
Vol 09 ◽  
Author(s):  
Tejas Patel ◽  
B.N. Suhagia

Background: Diabetes mellitus is major issue to public health as its prevalence is rising day by day. Synthetic agents available for the diabetic treatment are expensive or produce undesirable side effect on chronic use and some of them are not suitable during pregnancy. Herbal medicines accepted widely due to side effects and low cost. Objective: The aim of present study was to evaluate the activity of Withania coagulans extract using In-vitro and In-vivo model. Methods: Different three types of Withania coagulans extract were prepared using aqueous (W1), Alcohol (W2) and hydro-alcoholic (50:50) mixture (W3). In-vitro Anti-diabetic activity of the all three extracts evaluated using RINm5F Pancreatic beta cells.Further, n-vivo anti-diabetic evaluation performed by administering 50 mg/kg (p.o) aqueous extract for 7 days in Streptozotocin (STZ)-induced mice. Body weight of the animals was also determined to perform acute toxicity study. Results: The results of in –vitro cell based study indicated that among all three extract, aqueous extract (W1) of Withania coagulans showed potential increase in inulin release. The EC50 of the W1 (249.6 µg/L) which is compared with standard (Glibenclamide) EC50. From the results of In-vitro study, W1 subjected for acute toxicity study and the acute toxicity study results indicated LD50 of 50mg/kg. Diabetic rats treated with W1 extract at oral dose of 50 mg/kg for 7 days showed 34.17% reduction in blood glucose in comparison to untreated diabetic (STZ-induced) rats. Blood glucose levels of Standard treated (Glibenclamide) and control untreated. Conclusion: In conclusion, results of pancreatic beta cell based study showed increase in insulin release by administration of extract. Further aqueous extract (W1) was potentially reduced blood glucose level in STZ induced diabetic mice.


1997 ◽  
Vol 41 (5) ◽  
pp. 1082-1093 ◽  
Author(s):  
S M Daluge ◽  
S S Good ◽  
M B Faletto ◽  
W H Miller ◽  
M H St Clair ◽  
...  

1592U89, (-)-(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclo pentene-1-methanol, is a carbocyclic nucleoside with a unique biological profile giving potent, selective anti-human immunodeficiency virus (HIV) activity. 1592U89 was selected after evaluation of a wide variety of analogs containing a cyclopentene substitution for the 2'-deoxyriboside of natural deoxynucleosides, optimizing in vitro anti-HIV potency, oral bioavailability, and central nervous system (CNS) penetration. 1592U89 was equivalent in potency to 3'-azido-3'-deoxythymidine (AZT) in human peripheral blood lymphocyte (PBL) cultures against clinical isolates of HIV type 1 (HIV-1) from antiretroviral drug-naive patients (average 50% inhibitory concentration [IC50], 0.26 microM for 1592U89 and 0.23 microM for AZT). 1592U89 showed minimal cross-resistance (approximately twofold) with AZT and other approved HIV reverse transcriptase (RT) inhibitors. 1592U89 was synergistic in combination with AZT, the nonnucleoside RT inhibitor nevirapine, and the protease inhibitor 141W94 in MT4 cells against HIV-1 (IIIB). 1592U89 was anabolized intracellularly to its 5'-monophosphate in CD4+ CEM cells and in PBLs, but the di- and triphosphates of 1592U89 were not detected. The only triphosphate found in cells incubated with 1592U89 was that of the guanine analog (-)-carbovir (CBV). However, the in vivo pharmacokinetic, distribution, and toxicological profiles of 1592U89 were distinct from and improved over those of CBV, probably because CBV itself was not appreciably formed from 1592U89 in cells or animals (<2%). The 5'-triphosphate of CBV was a potent, selective inhibitor of HIV-1 RT, with Ki values for DNA polymerases (alpha, beta, gamma, and epsilon which were 90-, 2,900-, 1,200-, and 1,900-fold greater, respectively, than for RT (Ki, 21 nM). 1592U89 was relatively nontoxic to human bone marrow progenitors erythroid burst-forming unit and granulocyte-macrophage CFU (IC50s, 110 microM) and human leukemic and liver tumor cell lines. 1592U89 had excellent oral bioavailability (105% in the rat) and penetrated the CNS (rat brain and monkey cerebrospinal fluid) as well as AZT. Having demonstrated an excellent preclinical profile, 1592U89 has progressed to clinical evaluation in HIV-infected patients.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Allison M. Khoo ◽  
Sang Hyun Cho ◽  
Francisco J. Reynoso ◽  
Maureen Aliru ◽  
Kathryn Aziz ◽  
...  

2021 ◽  
Vol 19 ◽  
pp. 228080002198969
Author(s):  
Min-Xia Zhang ◽  
Wan-Yi Zhao ◽  
Qing-Qing Fang ◽  
Xiao-Feng Wang ◽  
Chun-Ye Chen ◽  
...  

The present study was designed to fabricate a new chitosan-collagen sponge (CCS) for potential wound dressing applications. CCS was fabricated by a 3.0% chitosan mixture with a 1.0% type I collagen (7:3(w/w)) through freeze-drying. Then the dressing was prepared to evaluate its properties through a series of tests. The new-made dressing demonstrated its safety toward NIH3T3 cells. Furthermore, the CCS showed the significant surround inhibition zone than empty controls inoculated by E. coli and S. aureus. Moreover, the moisture rates of CCS were increased more rapidly than the collagen and blank sponge groups. The results revealed that the CCS had the characteristics of nontoxicity, biocompatibility, good antibacterial activity, and water retention. We used a full-thickness excisional wound healing model to evaluate the in vivo efficacy of the new dressing. The results showed remarkable healing at 14th day post-operation compared with injuries treated with collagen only as a negative control in addition to chitosan only. Our results suggest that the chitosan-collagen wound dressing were identified as a new promising candidate for further wound application.


2021 ◽  
Vol 42 ◽  
pp. 3041-3045
Author(s):  
Rua J. Kadhim ◽  
Esraa H. Karsh ◽  
Zainab J. Taqi ◽  
Majid S. Jabir

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