scholarly journals Ligand-Tuning of the Stability of Pd(II) Conjugates with Cyanocobalamin

2021 ◽  
Vol 22 (15) ◽  
pp. 7973
Author(s):  
Dominika Porębska ◽  
Łukasz Orzeł ◽  
Dorota Rutkowska-Zbik ◽  
Grażyna Stochel ◽  
Rudi van Eldik

Besides the well-known functions performed by vitamin B12 (CblCN) in biochemical processes of the human body, an increasing interest has been raised by the possibility of its use as a transmembrane drug carrier, capable, among others, of enhancing the accumulation of inorganic cytostatics in cancer cells. The present study was aimed at determining the possibility of the formation of CblCN conjugates with Pd(II) complexes. A key aspect was their stability, which we attempted to tune by appropriate choice of ligands. Syntheses, spectroscopic analysis of postreaction systems and kinetic investigations of conjugate formation reactions, have been complemented by DFT modelling. The obtained results showed that ligand charge, geometry and electron affinity may have a significant impact on carrier binding and release leading to the activation of the Pd(II) complex. This provides a rationale to expect that with appropriate composition of the coordination sphere, it will be possible to extend the spectrum of less toxic inorganic chemotherapeutics.

2021 ◽  
Vol 33 (11) ◽  
pp. 2579-2588
Author(s):  
Mandeep Kaur ◽  
Aditya Wadhwa ◽  
Vineet Kumar

Nanomaterials of biological origin are very useful for drug delivery applications. The stability, biodegradability and biocompatibility of pectin nanomaterials in the human body make them an effective drug carrier. This review focus on different aspect of synthesis, drug encapsulation, drug release and safety of pectin-based nanomaterials. The nanomaterials can be used for the delivery of different hydrophilic and hydrophobic drugs to various organs. The release kinetics of drug loaded pectin-based nanoparticles can be studied in vitro as well as in vivo. The pectin-based nanomaterials have good pharmaco-kinetics and can ensure controlled drug delivery. However, the toxicity of pectin-based nanomaterials to human body needs to be evaluated carefully before industrial scale application.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Koshi Nishida ◽  
Toshifumi Tojo ◽  
Takeshi Kondo ◽  
Makoto Yuasa

AbstractPorphyrin derivatives accumulate selectively in cancer cells and are can be used as carriers of drugs. Until now, the substituents that bind to porphyrins (mainly at the meso-position) have been actively investigated, but the effect of the functional porphyrin positions (β-, meso-position) on tumor accumulation has not been investigated. Therefore, we investigated the correlation between the functional position of substituents and the accumulation of porphyrins in cancer cells using cancer cells. We found that the meso-derivative showed higher accumulation in cancer cells than the β-derivative, and porphyrins with less bulky substituent actively accumulate in cancer cells. When evaluating the intracellular distribution of porphyrin, we found that porphyrin was internalized by endocytosis and direct membrane permeation. As factors involved in these two permeation mechanisms, we evaluated the affinity between porphyrin-protein (endocytosis) and the permeability to the phospholipid bilayer membrane (direct membrane permeation). We found that the binding position of porphyrin affects the factors involved in the transmembrane permeation mechanisms and impacts the accumulation in cancer cells.


2021 ◽  
Vol 10 (1) ◽  
pp. 744-753
Author(s):  
Zahra Rahimzadeh ◽  
Seyed Morteza Naghib ◽  
Esfandyar Askari ◽  
Fatemeh Molaabasi ◽  
Ali Sadr ◽  
...  

Abstract In this paper, we use a simple and cheap approach for the synthesis of herceptin-conjugated graphene biosensor to detect the HER2-positive breast cancer cells. The bifunctional graphene-herceptin nanosheets are prepared from graphite by a simple ultrasonic-mediated technique. The prepared protein-mediated graphene is fully characterized. The results show the exfoliation of graphene layers in herceptin solution. Moreover, herceptin is effectively conjugated into the surface of graphene nanosheets. The synthesized herceptin-conjugated graphene is applied for breast cancer detection. The linear range of this biosensor is 1–80 cells, which is significant. The biosensor shows an excellent selectivity performance for detection of HER2-positive cancer cells. Likewise, the stability and functionality of the biosensor is about 40 days. Based on the results, this device is a promising candidate for rapid and selective detection of cancer cells.


MRS Bulletin ◽  
1990 ◽  
Vol 15 (1) ◽  
pp. 41-47 ◽  
Author(s):  
Nikola Kallay

The adhesion of particles at solid surfaces in liquid media has attracted the attention of scientists because of its various applications as well as the theoretical significance of the processes involved. Early studies were characterized either by poorly defined systems or limited by the properties of a few morphologically well-defined model colloids, such as latex dispersions. Consequently, results were either of semiquantitative nature or were related to some specific cases, which eluded general conclusions. New methods for preparing uniform particles of different compositions, shapes, and sizes make it possible to approach the problem in a more comprehensive manner. For example, to demonstrate difficulties caused by polydispersity, it is sufficient to mention that the electrostatic interaction energy between a plane surface and a particle is approximately proportional to the particle radius, yet the rate of deposition depends exponentially on the height of the energy barrier.In principle, static and dynamic approaches may be employed in the study of particle adhesion. The static method yields the force required to detach an adhered particle, while kinetic investigations of attachment and detachment give the rates of the respective processes. Both methods offer information on the stability of the system in terms of the bond strength of adhered solids. For small colloid particles, which are the subject of thermal random Brownian motion, the dynamic approach is more appropriate. This article emphasizes the kinetics of deposition and detachment of small colloid particles in liquid media.


Materials ◽  
2021 ◽  
Vol 14 (8) ◽  
pp. 1824
Author(s):  
Yu-Jyuan Wang ◽  
Pei-Ying Lin ◽  
Shu-Ling Hsieh ◽  
Rajendranath Kirankumar ◽  
Hsin-Yi Lin ◽  
...  

The purpose of this study was to use agar as a multifunctional encapsulating material to allow drug and ferromagnetism to be jointly delivered in one nanoparticle. We successfully encapsulated both Fe3O4 and doxorubicin (DOX) with agar as the drug carrier to obtain DOX-Fe3O4@agar. The iron oxide nanoparticles encapsulated in the carrier maintained good saturation of magnetization (41.9 emu/g) and had superparamagnetism. The heating capacity test showed that the specific absorption rate (SAR) value was 18.9 ± 0.5 W/g, indicating that the ferromagnetic nanoparticles encapsulated in the gel still maintained good heating capacity. Moreover, the magnetocaloric temperature could reach 43 °C in a short period of five minutes. In addition, DOX-Fe3O4@agar reached a maximum release rate of 85% ± 3% in 56 min under a neutral pH 7.0 to simulate the intestinal environment. We found using fluorescent microscopy that DOX entered HT-29 human colon cancer cells and reduced cell viability by 66%. When hyperthermia was induced with an auxiliary external magnetic field, cancer cells could be further killed, with a viability of only 15.4%. These results show that agar is an efficient multiple-drug carrier, and allows controlled drug release. Thus, this synergic treatment has potential application value for biopharmaceutical carrier materials.


2021 ◽  
Vol 8 (4) ◽  
pp. 783-796
Author(s):  
H. W. Salih ◽  
◽  
A. Nachaoui ◽  

In this work, we study an impulsive mathematical model proposed by Chavez et al. [1] to describe the dynamics of cancer growth and HIV infection, when chemotherapy and HIV treatment are combined. To better understand these complex biological phenomena, we study the stability of equilibrium points. To do this, we construct an appropriate Lyapunov function for the first equilibrium point while the indirect Lyapunov method is used for the second one. None of the equilibrium points obtained allow us to study the stability of the chemotherapeutic dynamics, we then propose a bifurcation of the model and make a study of the bifurcated system which contributes to a better understanding of the underlying biochemical processes which govern this highly active antiretroviral therapy. This shows that this mathematical model is sufficiently realistic to formulate the impact of this treatment.


2017 ◽  
Vol 408 ◽  
pp. 164-173 ◽  
Author(s):  
O. Bashari ◽  
B. Redko ◽  
A. Cohen ◽  
G. Luboshits ◽  
G. Gellerman ◽  
...  

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1911
Author(s):  
Anastasiya Oshchepkova ◽  
Oleg Markov ◽  
Evgeniy Evtushenko ◽  
Alexander Chernonosov ◽  
Elena Kiseleva ◽  
...  

The main advantage of extracellular vesicles (EVs) as a drug carrier system is their low immunogenicity and internalization by mammalian cells. EVs are often considered a cell-specific delivery system, but the production of preparative amounts of EVs for therapeutic applications is challenging due to their laborious isolation and purification procedures. Alternatively, mimetic vesicles prepared from the cellular plasma membrane can be used in the same way as natural EVs. For example, a cytoskeleton-destabilizing agent, such as cytochalasin B, allows the preparation of membrane vesicles by a series of centrifugations. Here, we prepared cytochalasin-B-inducible nanovesicles (CINVs) of various cellular origins and studied their tropism in different mammalian cells. We observed that CINVs derived from human endometrial mesenchymal stem cells exhibited an enhanced affinity to epithelial cancer cells compared to myeloid, lymphoid or neuroblastoma cancer cells. The dendritic cell-derived CINVs were taken up by all studied cell lines with a similar efficiency that differed from the behavior of DC-derived EVs. The ability of cancer cells to internalize CINVs was mainly determined by the properties of recipient cells, and the cellular origin of CINVs was less important. In addition, receptor-mediated interactions were shown to be necessary for the efficient uptake of CINVs. We found that CINVs, derived from late apoptotic/necrotic cells (aCINVs) are internalized by in myelogenous (K562) 10-fold more efficiently than CINVs, and interact much less efficiently with melanocytic (B16) or epithelial (KB-3-1) cancer cells. Finally, we found that CINVs caused a temporal and reversible drop of the rate of cell division, which restored to the level of control cells with a 24 h delay.


2020 ◽  
Author(s):  
Chunying Liu ◽  
Xuejing Lin ◽  
Changqing Su

Extracellular vesicles (EVs) can deliver many types of drugs with their natural source material transport properties, inherent long-term blood circulation capabilities and excellent biocompatibility, and have great potential in the field of drug carrier. Modification of the content and surface of EVs according to the purpose of treatment has become a research focus to improve the drug load and the targeting of EVs. EVs can maximize the stability of the drugs, prevent immune clearance and achieve accurate delivery. Therefore, EVs can be described as \" stealth transport aircrafts \" for drugs. This chapter will respectively introduce the application of natural EVs as cell substitutes in cell therapy and engineered EVs as carriers of nucleic acids, proteins, small molecule drugs and therapeutic viral particles in disease treatment. It will also explain the drug loading and modification strategies of EVs, the source and characteristics of EVs. In addition, the commercialization progress of EVs drugs will be mentioned here, and the problems in their applications will be discussed in conjunction with the application of EVs in the treatment of COVID-19.


Author(s):  
Marta Olivares ◽  
Martin Albrecht

Pyridyl-triazolylidene ligands with variable donor properties were used as tunable ligands at a dihydride iridium(III) center. The straightforward synthesis of this type of ligand allows for an easy incorporation of electron donating substituents in different positions of the pyridine ring or different functional groups such as esters, alkoxy or aliphatic chains on the C4 position of the triazole heterocycle. The stability of these hydride metal systems allowed these complexes to be used as models for studying the influence of the ligand modifications on hydride reactivity. Spectroscopic analysis provided unambiguous structural assignment of the dihydride system. Modulation of the electronic properties of the wingtip substituents did not appreciably alter the reactivity of the hydrides. Reactivity studies using acids with a wide range of pKa values indicated a correlation between hydride reactivity and acidity and showed exclusive reactivity towards the less shielded hydride trans to the carbene carbon rather than the more shielded hydride trans to the pyridine ring, suggesting that the trans effect is more relevant in these reactions than the NMR spectroscopically deduced hydridic character.


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