Targeting Regulation of Dually Modified Liposomes by Polyethylene Glycol Length of Vesicle Surface

2019 ◽  
Vol 15 (12) ◽  
pp. 2413-2427
Author(s):  
Xiaoying Liu ◽  
Shukun Tang ◽  
Yuncui Liu ◽  
Dandan Hu ◽  
Changmei Zhang ◽  
...  

With aging of population, changing of living habits, and intake of high-fat diet, more and more people have been suffering from cardio-cerebral apoplexy. The synchronous treatment of cardio-cerebral conditions based on an integral strategy may bring benefit to the better clinical efficacy. The simultaneously-targeting delivery of active molecules by nanoscale carriers to heart and brain remains unmet problem. The physiological difference of targets between heart and brain makes it a huge challenge which one targeting ligand modification acquires the delivery of two organs and treatment, simultaneously. Traditionally, dually targeting strategies are introduced to enhance the selectivity for one aimed tissue and delivery efficiency of these particles. However, the interference between two targeting ligands on the surface of nanoscale carriers may influence the affinity of these ligands with their receptors or transporters, resulting to the change distribution of carriers. Herein, we observed that how anti-cardiac troponin I (cTnI) antibody (Ab) conjugated with the linker, polyethylene glycol (PEG), on the surface of liposomes influenced the affinity of mannose derivatives with transporter and regulated distribution of these vesicles in the heart and brain. The dually targeting liposomes can target to the heart and brain tissue simultaneously by the regulation length of PEG chain linking with p -pentanoic acid phenyl-α-D-acetylmannosamine (Ac4MAN). These results may bring benefit to design the multi-modification of nanocarriers and the treatment of cardio-cerebral diseases.

RSC Advances ◽  
2015 ◽  
Vol 5 (71) ◽  
pp. 57725-57734 ◽  
Author(s):  
Yiping Zeng ◽  
Zhangyou Yang ◽  
Shenglin Luo ◽  
Hong Li ◽  
Cong Liu ◽  
...  

A fast, facile and mass production method was reported to obtain stable and disperse polyethylene glycol (PEG) modified nanographene (NGO-PEG). Branched polyethylenimine (BPEI) was used to modify the NGO-PEG (NGO-PEG-BPEI) for further application.


2021 ◽  
Vol 10 (9) ◽  
Author(s):  
Lian Liang ◽  
Guozhen Zhang ◽  
Hui Li ◽  
Cheng Cheng ◽  
Tao Jin ◽  
...  

Background To investigate the therapeutic potential of combined therapy with polyethylene glycol‐20k (PEG‐20k) and MCC950 on post‐resuscitation myocardial function in a rat model of cardiac arrest. Methods and Results Thirty rats were randomized into 5 groups: Sham, Control, PEG‐20k, MCC950, PEG‐20k+ MCC950. Except for sham, animals were subjected to 6 minutes of ventricular fibrillation followed by 8 minutes cardiopulmonary resuscitation. Two milliliters PEG‐20k was administered by intravenous injection coincident with the start of cardiopulmonary resuscitation; MCC950 (10 mg/kg), a highly selective NLRP3 inflammasome inhibitor, was delivered immediately after restoration of spontaneous circulation. Myocardial function, sublingual microcirculation, mitochondrial function, plasma cardiac troponin I, and interleukin‐1β, expression of proteins in SIRT1 (sirtuin 1)/PGC‐1α (peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha) and NLRP3 (the NOD‐like receptor family protein 3) inflammasome pathways were evaluated. Following cardiopulmonary resuscitation, myocardial function was compromised with a significantly decreased cardiac output, ejection fraction, and increased myocardial performance index, cardiac troponin I. Sublingual microcirculation was disturbed with impaired perfused vessel density and microvascular flow index. Cardiac arrest reduced mitochondrial routine respiration, Complex I‐linked respiration, respiratory control rates and oxidative phosphorylation coupling efficiency. PEG‐20k or MCC950 alone restored mitochondrial respiratory function, restituted sublingual microcirculation, and preserved myocardial function, whereas a combination of PEG‐20k and MCC950 further improved these aspects. PEG‐20k restored the expression of SIRT1 and PGC‐1α, and blunted activation of NLRP3 inflammasomes. MCC950 suppressed expression of cleaved‐caspase‐1/pro‐caspase‐1, ASC (apoptosis‐associated speck‐like protein), GSDMD [gasdermin d], and interleukin‐1β. Conclusions Combined therapy with PEG‐20k and MCC950 is superior to either therapy alone for preserving post‐resuscitated myocardial function, restituting sublingual microcirculation at restoration of spontaneous circulation at 6 hours. The responsible mechanisms involve upregulated expression of SIRT1/PGC1‐α in tandem with inhibition of NLRP3 inflammasomes.


2002 ◽  
Vol 126 (5) ◽  
pp. 606-609
Author(s):  
Ronald J. Knoblock ◽  
Christopher M. Lehman ◽  
Ruth A. Smith ◽  
Fred S. Apple ◽  
William L. Roberts

Abstract A number of classes of endogenous antibodies, including heterophile, rheumatoid factor, and autoantibodies, can interfere with immunoassay measurements of many different analytes. Heterophile and rheumatoid factor antibody interferences have been described previously for the AxSYM cardiac troponin I assay. Several commercial products have been developed to neutralize heterophile antibody interferences. We describe a patient with multiple apparently falsely elevated cardiac troponin I results that were unique to the AxSYM analyzer. These cardiac troponin I results diluted linearly. When treated with 2 different heterophile-blocking reagents, the magnitudes of the falsely elevated results increased 17- and 26-fold, and these results also demonstrated dilution linearity. This interfering substance could be removed by passage through an immobilized protein A column and by polyethylene glycol precipitation. It does not appear to be a classic heterophile antibody, nor is it a paraprotein. Laboratorians must remain constantly vigilant for immunoassay interferences that lead to clinically significant inaccurate results and must recognize that accepted methods for detecting and neutralizing the interference may be ineffective.


Pharmaceutics ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 423 ◽  
Author(s):  
Ji Hee Kang ◽  
Young Tag Ko

Mitochondria are membrane-enclosed organelles present in most eukaryotic cells, described as “power houses of the cell”. The mitochondria can be a target for inducing cancer cell death and for developing strategies to bypass multi drug resistance (MDR) mechanisms. 4-Carboxybutyl triphenylphosphonium bromide-polyethylene glycol-distearoylphosphatidylethanolamine (TPP-DSPE-PEG) and dequalinium-polyethylene glycol-distearoylphosphatidylethanolamine (DQA-DSPE-PEG) were synthesized as mitochondriotropic molecules. Mitochondria-targeting liposomes carrying resveratrol were constructed by modifying the liposome’s surface with TPP-PEG or DQA-PEG, resulting in TLS (Res) and DLS (Res), respectively, with the aim to obtain longer blood circulation and enhanced permeability and retention (EPR). Both TLS (Res) and DLS (Res) showed dimensions of approximately 120 nm and a slightly positive zeta potential. The enhanced cellular uptake and selective accumulation of TLS (Res) and DLS (Res) into the mitochondria were demonstrated by behavioral observation of rhodamine-labeled TLS or DLS, using confocal microscopy, and by resveratrol quantification in the intracellular organelle, using LC–MS/MS. Furthermore, TLS (Res) and DLS (Res) induced cytotoxicity of cancer cells by generating reactive oxygen species (ROS) and by dissipating the mitochondrial membrane potential. Our results demonstrated that TLS (Res) and DLS (Res) could provide a potential strategy to treat cancers by mitochondrial targeting delivery of therapeutics and stimulation of the mitochondrial signaling pathway.


2020 ◽  
Vol 49 (8) ◽  
pp. 2273-2290 ◽  
Author(s):  
Zheng Li ◽  
Chen Xiao ◽  
Tuying Yong ◽  
Zifu Li ◽  
Lu Gan ◽  
...  

This tutorial review summarizes the influence of nanomedicine mechanical properties on drug delivery efficiency, antitumor efficacy and safety.


2013 ◽  
Vol 386 (8) ◽  
pp. 733-745 ◽  
Author(s):  
Jae-Hyung Park ◽  
Yoon Jung Choi ◽  
Yong Woon Kim ◽  
Sang Pyo Kim ◽  
Ho-Chan Cho ◽  
...  

2019 ◽  
Vol 12 (5) ◽  
pp. e229217 ◽  
Author(s):  
Elisabetta Caredda ◽  
Roberto Rosso ◽  
Carlo Capristo ◽  
Paolo Montaldo

Serum biomarkers of myocardial damage are commonly used in babies after perinatal asphyxia. We present a case report of a persistently troponin I elevation without evidence of clinical or instrumental signs of myocardial ischaemia in a baby with perinatal asphyxia. When the blood was mixed with polyethylene glycol we found that the troponin I levels were falsely elevated due to interfering antibodies. This case shows that analytical errors may still occur despite modern immunoassay systems and underlines the need for further investigations to identify false-positive values in case of disagreement between clinical conditions and laboratory values.


Author(s):  
Kuixiong Gao ◽  
Randal E. Morris ◽  
Bruce F. Giffin ◽  
Robert R. Cardell

Several enzymes are involved in the regulation of anabolic and catabolic pathways of carbohydrate metabolism in liver parenchymal cells. The lobular distribution of glycogen synthase (GS), phosphoenolpyruvate carboxykinase (PEPCK) and glycogen phosphorylase (GP) was studied by immunocytochemistry using cryosections of normal fed and fasted rat liver. Since sections of tissue embedded in polyethylene glycol (PEG) show good morphological preservation and increased detectability for immunocytochemical localization of antigenic sites, and semithin sections of Visio-Bond (VB) embedded tissue provide higher resolution of cellular structure, we applied these techniques and immunogold-silver stain (IGSS) for a more accurate localization of hepatic carbohydrate metabolic enzymes.


Author(s):  
Dai Dalin ◽  
Guo Jianmin

Lipid cytochemistry has not yet advanced far at the EM level. A major problem has been the loss of lipid during dehydration and embedding. Although the adoption of glutaraldehyde and osmium tetroxide accelerate the chemical reaction of lipid and osmium tetroxide can react on the double bouds of unsaturated lipid to from the osmium black, osmium tetroxide can be reduced in saturated lipid and subsequently some of unsaturated lipid are lost during dehydration. In order to reduce the loss of lipid by traditional method, some researchers adopted a few new methods, such as the change of embedding procedure and the adoption of new embedding media, to solve the problem. In a sense, these new methods are effective. They, however, usually require a long period of preparation. In this paper, we do research on the fiora nectary strucure of lauraceae by the rapid-embedding method wwith PEG under electron microscope and attempt to find a better method to solve the problem mentioned above.


Sign in / Sign up

Export Citation Format

Share Document