scholarly journals Effects of Surface Protein Adsorption on the Distribution and Retention of Intratumorally Administered Gold Nanoparticles

2020 ◽  
Author(s):  
Rossana Terracciano ◽  
Aobo Zhang ◽  
E. Brian Butler ◽  
Danilo Demarchi ◽  
Jason H. Hafner ◽  
...  
Keyword(s):  
Treatment Modalities ◽  
Emission Spectrometry ◽  
Limiting Factor ◽  
High Resolution Computed Tomography ◽  
Quantitative Ct ◽  
Heterogeneous Distribution ◽  
Significant Difference ◽  
Intratumoral Distribution

Heterogeneous distribution of delivery or treatment modalities within the tumor mass is a crucial limiting factor for a vast range of theranostic applications. Understanding the interactions between a nanomaterial and the tumor microenvironment will help to overcome challenges associated with tumor heterogeneity as well as the clinical translation of nanotheranostic materials. This study aims to evaluate the influence of protein surface adsorption on gold nanoparticle (GNP) biodistribution using high resolution Computed Tomography (CT) preclinical imaging in C57BL/6 mice harboring Lewis Lung Carcinoma (LLC) tumors. LLC provides a valuable model for study due to its highly heterogenous nature which makes drug delivery to the tumor challenging. By controlling the adsorption of proteins on the GNP surface, we hypothesize that we can influence the intratumoral distribution pattern and particle retention. We performed an in vitro study to evaluate the uptake of GNPs by LLC cells and an in vivo study to assess and quantify the GNP biodistribution by injecting concentrated GNPs citrate stabilized or passivated with Bovine Serum Albumin (BSA) intratumorally into LLC solid tumors. Quantitative CT and Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES) results both confirm the presence of particles in the tumor 9 days post-injection (n=8 mice/group). Significant difference is highlighted between citrate-GNP and BSA-GNP groups (**p < 0.005, Tukey’s multiple comparisons test), confirming the protein corona of GNPs modifies intratumoral distribution and retention of the particles. In conclusion, our investigations show that the surface passivation of GNPs influences the mechanism of cellular uptake and intratumoral distribution in vivo highlighting the spatial heterogeneity of the solid tumor.

scholarly journals Effects of Surface Protein Adsorption on the Distribution and Retention of Intratumorally Administered Gold Nanoparticles

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 216
Author(s):  
Rossana Terracciano ◽  
Aobo Zhang ◽  
E. Brian Butler ◽  
Danilo Demarchi ◽  
Jason H. Hafner ◽  
...  
Keyword(s):  
Treatment Modalities ◽  
Emission Spectrometry ◽  
Limiting Factor ◽  
High Resolution Computed Tomography ◽  
Quantitative Ct ◽  
Heterogeneous Distribution ◽  
Significant Difference ◽  
Intratumoral Distribution

The heterogeneous distribution of delivery or treatment modalities within the tumor mass is a crucial limiting factor for a vast range of theranostic applications. Understanding the interactions between a nanomaterial and the tumor microenvironment will help to overcome challenges associated with tumor heterogeneity, as well as the clinical translation of nanotheranostic materials. This study aims to evaluate the influence of protein surface adsorption on gold nanoparticle (GNP) biodistribution using high-resolution computed tomography (CT) preclinical imaging in C57BL/6 mice harboring Lewis lung carcinoma (LLC) tumors. LLC provides a valuable model for study due to its highly heterogenous nature, which makes drug delivery to the tumor challenging. By controlling the adsorption of proteins on the GNP surface, we hypothesize that we can influence the intratumoral distribution pattern and particle retention. We performed an in vitro study to evaluate the uptake of GNPs by LLC cells and an in vivo study to assess and quantify the GNP biodistribution by injecting concentrated GNPs citrate-stabilized or passivated with bovine serum albumin (BSA) intratumorally into LLC solid tumors. Quantitative CT and inductively coupled plasma optical emission spectrometry (ICP-OES) results both confirm the presence of particles in the tumor 9 days post-injection (n = 8 mice/group). A significant difference is highlighted between citrate-GNP and BSA-GNP groups (** p < 0.005, Tukey’s multiple comparisons test), confirming that the protein corona of GNPs modifies intratumoral distribution and retention of the particles. In conclusion, our investigations show that the surface passivation of GNPs influences the mechanism of cellular uptake and intratumoral distribution in vivo, highlighting the spatial heterogeneity of the solid tumor.

Cytological changes induced by platinum-thymine in sarcoma-180 cells: Electron microscopy study

1990 ◽  
Vol 48 (3) ◽  
pp. 290-291
Author(s):  
Gustav Ofosu
Keyword(s):  
Mammalian Cells ◽  
Antitumor Agent ◽  
Microscopy Study ◽  
Electron Microscopy Study ◽  
Limiting Factor ◽  
Sarcoma 180 ◽  
Electron Microscopic ◽  
Cytological Changes

Platinum-thymine has been found to be a potent antitumor agent, which is quite soluble in water, and lack nephrotoxicity as the dose-limiting factor. The drug has been shown to interact with DNA and inhibits DNA, RNA and protein synthesis in mammalian cells in vitro. This investigation was undertaken to elucidate the cytotoxic effects of piatinum-thymine on sarcoma-180 cells in vitro ultrastructurally, Sarcoma-180 tumor bearing mice were treated with intraperitoneal injection of platinum-thymine 40mg/kg. A concentration of 60μg/ml dose of platinum-thymine was used in in vitro experiments. Treatments were at varying time intervals of 3, 7 and 21 days for in vivo experiments, and 30, 60 and 120 min., 6, 12, and 24th in vitro. Controls were not treated with platinum-thymine.Electron microscopic analyses of the treated cells in vivo and in vitro showed drastic cytotoxic effect.

An Attempt at Biological Control of Blossom Blight of Rose Caused by Botrytis cinerea Using some Local Trichoderma spp. Strains

2020 ◽  
Vol 55 (1) ◽  
pp. 27-34
Author(s):  
G. Zadehdabagh ◽  
K. Karimi ◽  
M. Rezabaigi ◽  
F. Ajamgard
Keyword(s):  
Botrytis Cinerea ◽  
Mycelial Growth ◽  
Limiting Factor ◽  
Dual Culture ◽  
Trichoderma Spp ◽  
Khuzestan Province ◽  
Inhibitory Potential ◽  
Cut Rose

The northern of Khuzestan province in Iran is mainly considered as one of the major areas of miniature rose production. Blossom blight caused by Botrytis cinerea has recently become a serious limiting factor in rose production in pre and post-harvest. In current study, an attempt was made to evaluate the inhibitory potential of some local Trichoderma spp. strains against B. cinerea under in vitro and in vivo conditions. The in vitro results showed that all Trichoderma spp. strains were significantly able to reduce the mycelial growth of the pathogen in dual culture, volatile and non-volatile compounds tests compared with control, with superiority of T. atroviride Tsafi than others. Under in vivo condition, the selected strain of T. atroviride Tsafi had much better performance than T. harzianum IRAN 523C in reduction of disease severity compared with the untreated control. Overall, the findings of this study showed that the application of Trichoderma-based biocontrol agents such as T. atroviride Tsafi can be effective to protect cut rose flowers against blossom blight.

scholarly journals The Effectiveness of Candidate Probiotic Bacteria to Control Vibriosis Disease

2017 ◽  
Vol 5 (2) ◽  
pp. 1
Author(s):  
Mulyati Mulyati ◽  
Suryati Suryati ◽  
Irfani Baga
Keyword(s):  
Survival Rate ◽  
Sea Water ◽  
Challenge Test ◽  
Probiotic Bacteria ◽  
Pathogenicity Test ◽  
Inhibitory Ability ◽  
Significant Difference ◽  
Portunid Crab

The study aims to isolate, characterize, and examine probiotic bacteria's inhibitory ability against Vibrio harveyi bacteria, both in-vitro and in vivo. Methods used in the study consist of 1) An Isolation of Candidate Probiotic Bacteria, 2) An Antagonistic Test of Candidate Probiotic Bacteria in vitro, 3) An Identification of Bacteria, 4) A Pathogenicity Test of Candidate Probiotic Bacteria, 5) An Antagonistic Test of Candidate Probiotic Bacteria against V. harveyi in vivo. According to the isolation of candidate probiotic bacteria, there are 18 isolated candidate probiotic. After being tested for its inhibitory ability in vitro, there are 8 isolates with zone of inhibition as follows: isolate MM 7 from intestine (22 mm), isolate MM 6 from intestine (12 mm), isolate MM 10 from sea water (10 mm), isolate MM 5 from intestine (9 mm), isolate MM 4 from intestine (8 mm), isolate MM 3 from intestine (7 mm), isolate MM 2.2 from intestine (7 mm), isolate MM 2.1 from intestine (7 mm). Eight genera of the candidate probiotic bacteria is derived from Portunid crab, they are Staphylococcus, Streptococcus, bacillus, vibrio, Alcaligenes, Lactobacillus, micrococcus. Before proceeding the V. harveyi bacterial challenge test in vivo, three potential isolates consisting of MM6, MM7 and MM10 as the probiotic bacteria are pathogenicity-tested against V. harveyi. The survival rate of Portunid crab on pathogenicity test using MM6, MM7 and MM10 generates 91.11-100%, while the control generates 100% survival rate. Variance analysis result through post-hoc Tukey's Honest Significant Difference (HSD) test at 95% confidence interval indicates that isolate MM7 and MM10 are significantly able to increase hatchling Portunid crab's survival rate.

scholarly journals Inhibitory Effects of a Reengineered Anthrax Toxin on Canine Oral Mucosal Melanomas

Toxins ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 157 ◽  
Author(s):  
Adriana Tomoko Nishiya ◽  
Marcia Kazumi Nagamine ◽  
Ivone Izabel Mackowiak da Fonseca ◽  
Andrea Caringi Miraldo ◽  
Nayra Villar Scattone ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Evaluation Criteria ◽  
Anthrax Toxin ◽  
Treatment Modalities ◽  
Inhibitory Effects ◽  
Upa Receptor ◽  
New Treatment ◽  
Oral Malignancy

Canine oral mucosal melanomas (OMM) are the most common oral malignancy in dogs and few treatments are available. Thus, new treatment modalities are needed for this disease. Bacillus anthracis (anthrax) toxin has been reengineered to target tumor cells that express urokinase plasminogen activator (uPA) and metalloproteinases (MMP-2), and has shown antineoplastic effects both, in vitro and in vivo. This study aimed to evaluate the effects of a reengineered anthrax toxin on canine OMM. Five dogs bearing OMM without lung metastasis were included in the clinical study. Tumor tissue was analyzed by immunohistochemistry for expression of uPA, uPA receptor, MMP-2, MT1-MMP and TIMP-2. Animals received either three or six intratumoral injections of the reengineered anthrax toxin prior to surgical tumor excision. OMM samples from the five dogs were positive for all antibodies. After intratumoral treatment, all dogs showed stable disease according to the canine Response Evaluation Criteria in Solid Tumors (cRECIST), and tumors had decreased bleeding. Histopathology has shown necrosis of tumor cells and blood vessel walls after treatment. No significant systemic side effects were noted. In conclusion, the reengineered anthrax toxin exerted inhibitory effects when administered intratumorally, and systemic administration of this toxin is a promising therapy for canine OMM.

scholarly journals Multimodal Diagnostics of Microrheologic Alterations in Blood of Coronary Heart Disease and Diabetic Patients

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 76
Author(s):  
Anastasia Maslianitsyna ◽  
Petr Ermolinskiy ◽  
Andrei Lugovtsov ◽  
Alexandra Pigurenko ◽  
Maria Sasonko ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Optical Methods ◽  
Diabetic Patients ◽  
Aggregation Index ◽  
Significant Difference

Coronary heart disease (CHD) has serious implications for human health and needs to be diagnosed as early as possible. In this article in vivo and in vitro optical methods are used to study blood properties related to the aggregation of red blood cells in patients with CHD and comorbidities such as type 2 diabetes mellitus (T2DM). The results show not only a significant difference of the aggregation in patients compared to healthy people, but also a correspondence between in vivo and in vitro parameters. Red blood cells aggregate in CHD patients faster and more numerously; in particular the aggregation index increases by 20 ± 7%. The presence of T2DM also significantly elevates aggregation in CHD patients. This work demonstrates multimodal diagnostics and monitoring of patients with socially significant pathologies.

scholarly journals A Tumbling Magnetic Microrobot System for Biomedical Applications

Micromachines ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 861
Author(s):  
Elizabeth E. Niedert ◽  
Chenghao Bi ◽  
Georges Adam ◽  
Elly Lambert ◽  
Luis Solorio ◽  
...  
Keyword(s):  
Ultrasound Imaging ◽  
Biomedical Applications ◽  
Imaging System ◽  
Ex Vivo ◽  
Negative Control ◽  
Circular Path ◽  
Rotational Axis ◽  
Significant Difference

A microrobot system comprising an untethered tumbling magnetic microrobot, a two-degree-of-freedom rotating permanent magnet, and an ultrasound imaging system has been developed for in vitro and in vivo biomedical applications. The microrobot tumbles end-over-end in a net forward motion due to applied magnetic torque from the rotating magnet. By turning the rotational axis of the magnet, two-dimensional directional control is possible and the microrobot was steered along various trajectories, including a circular path and P-shaped path. The microrobot is capable of moving over the unstructured terrain within a murine colon in in vitro, in situ, and in vivo conditions, as well as a porcine colon in ex vivo conditions. High-frequency ultrasound imaging allows for real-time determination of the microrobot’s position while it is optically occluded by animal tissue. When coated with a fluorescein payload, the microrobot was shown to release the majority of the payload over a 1-h time period in phosphate-buffered saline. Cytotoxicity tests demonstrated that the microrobot’s constituent materials, SU-8 and polydimethylsiloxane (PDMS), did not show a statistically significant difference in toxicity to murine fibroblasts from the negative control, even when the materials were doped with magnetic neodymium microparticles. The microrobot system’s capabilities make it promising for targeted drug delivery and other in vivo biomedical applications.

Role of Apolipoprotein A-I in Protecting against Endotoxin Toxicity

2004 ◽  
Vol 36 (6) ◽  
pp. 419-424 ◽  
Author(s):  
Juan Ma ◽  
Xue-Ling Liao ◽  
Bin Lou ◽  
Man-Ping Wu
Keyword(s):  
Survival Time ◽  
Binding Capacity ◽  
Density Lipoprotein ◽  
Mtt Method ◽  
Apolipoprotein A ◽  
Plasma Fraction ◽  
Significant Difference ◽  
In Vivo Effects

Abstract High density lipoprotein (HDL) binds lipopolysaccharide (LPS or endotoxin) and neutralizes its toxicity. We investigated the function of Apolipoprotein A-I (ApoA-I), a major apolipoprotein in HDL, in this process. Mouse macrophages were incubated with LPS, LPS+ApoA-I, LPS+ApoA-I+LFF (lipoprotein-free plasma fraction d>1.210 g/ml), LPS+HDL, LPS+HDL+LFF, respectively. MTT method was used to detect the mortality of L-929 cells which were attacked by the release-out cytokines in LPS-activated macrophages. It was found that ApoA-I significantly decreased L-929 cells mortality caused by LPS treatment (LPS vs. LPS+ApoA-I, P<0.05) and this effect became even more significant when LFF was utilized (LPS vs. LPS+ApoA-I+LFF, P<0.01; LPS vs. LPS+HDL+LFF, P<0.01). There was no significant difference between LPS+ApoA-I+LFF and LPS+HDL+LFF treatment, indicating that ApoA-I was the main factor. We also investigated in vivo effects of ApoA-I on mouse mortality rate and survival time after LPS administration. We found that the mortality in LPS+ApoA-I group (20%) and in LPS+ApoA-I+LFF group (10%) was significantly lower than that in LPS group (80%) (P<0.05, P<0.01, respectively); the survival time was (43.20 ± 10.13) h in LPS+ApoA-I group and (46.80 ± 3.79) h in LPS+ApoA-I+LFF group, which were significantly longer than that in LPS group (16.25 ± 17.28) h (P<0.01). We also carried out in vitro binding study to investigate the binding capacity of ApoA-I and ApoA-I+LFF to fluorescence labeled LPS (FITC-LPS). It was shown that both ApoA-I and ApoA-I+LFF could bind with FITC-LPS, however, the binding capacity of ApoA-I+LFF to FITC-LPS (64.47 ± 8.06) was significantly higher than that of ApoA-I alone (24.35 ± 3.70) (P<0.01). The results suggest that: (1) ApoA-I has the ability to bind with and protect against LPS; (2) LFF enhances the effect of ApoA-I; (3) ApoA-I is the major contributor for HDL anti-endotoxin function.

scholarly journals In VivoVisualization of Heterogeneous Intratumoral Distribution of Hypoxia-Inducible Factor-1αActivity by the Fusion of High-Resolution SPECT and Morphological Imaging Tests

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Hirofumi Fujii ◽  
Masayuki Yamaguchi ◽  
Kazumasa Inoue ◽  
Yasuko Mutou ◽  
Masashi Ueda ◽  
...  
Keyword(s):  
High Resolution ◽  
Ex Vivo ◽  
Hypoxia Inducible Factor ◽  
Chimeric Protein ◽  
Small Animal ◽  
Ct Scanner ◽  
Heterogeneous Distribution ◽  
Fusion Images ◽  
Intratumoral Distribution

Purpose. We aimed to clearly visualize heterogeneous distribution of hypoxia-inducible factor 1α(HIF) activity in tumor tissuesin vivo.Methods. We synthesized of125I-IPOS, a125I labeled chimeric protein probe, that would visualize HIF activity. The biodistribution of125I-IPOS in FM3A tumor-bearing mice was evaluated. Then, the intratumoral localization of this probe was observed by autoradiography, and it was compared with histopathological findings. The distribution of125I-IPOS in tumors was imaged by a small animal SPECT/CT scanner. The obtainedin vivoSPECT-CT fusion images were compared withex vivoimages of excised tumors. Fusion imaging with MRI was also examined.Results.125I-IPOS well accumulated in FM3A tumors. The intratumoral distribution of125I-IPOS by autoradiography was quite heterogeneous, and it partially overlapped with that of pimonidazole. High-resolution SPECT-CT fusion images successfully demonstrated the heterogeneity of125I-IPOS distribution inside tumors. SPECT-MRI fusion images could give more detailed information about the intratumoral distribution of125I-IPOS.Conclusion. High-resolution SPECT images successfully demonstrated heterogeneous intratumoral distribution of125I-IPOS. SPECT-CT fusion images, more favorably SPECT-MRI fusion images, would be useful to understand the features of heterogeneous intratumoral expression of HIF activityin vivo.

scholarly journals In Vivo Radioprotective Activity of Cell-Permeable Bifunctional Antioxidant Enzyme GST-TAT-SOD against Whole-Body Ionizing Irradiation in Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Jianru Pan ◽  
Huocong He ◽  
Ying Su ◽  
Guangjin Zheng ◽  
Junxin Wu ◽  
...  
Keyword(s):  
Growth Rate ◽  
Antioxidant Activity ◽  
Body Weight ◽  
Whole Body ◽  
White Pulp ◽  
Radioprotective Activity ◽  
Significant Difference ◽  
Wbc Count

GST-TAT-SOD was the fusion of superoxide dismutase (SOD), cell-permeable peptide TAT, and glutathione-S-transferase (GST). It was proved to be a potential selective radioprotector in vitro in our previous work. This study evaluated the in vivo radioprotective activity of GST-TAT-SOD against whole-body irradiation. We demonstrated that intraperitoneal injection of 0.5 ml GST-TAT-SOD (2 kU/ml) 2 h before the 6 Gy whole-body irradiation in mice almost completely prevented the splenic damage. It could significantly enhance the splenic antioxidant activity which kept the number of splenic white pulp and consequently resisted the shrinkage of the spleen. Moreover, the thymus index, hepatic antioxidant activity, and white blood cell (WBC) count of peripheral blood in irradiated mice pretreated with GST-TAT-SOD also remarkably increased. Although the treated and untreated irradiated mice showed no significant difference in the growth rate of animal body weight at 7 days postirradiation, the highest growth rate of body weight was observed in the GST-TAT-SOD-pretreated group. Furthermore, GST-TAT-SOD pretreatment increased resistance against 8 Gy whole-body irradiation and enhanced 30 d survival. The overall effect of GST-TAT-SOD seemed to be a bit more powerful than that of amifostine. In conclusion, GST-TAT-SOD would be a safe and potentially promising radioprotector.

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