scholarly journals Estimating the Two Graph Dextran-Stearic Acid-Spermine Polymers Based on Iron Oxide Nanoparticles as Carrier for Gene Delivery

Author(s):  
Mehrnoosh Kazemi Ashtiyani ◽  
Behnam Hajipour-Verdom ◽  
Mohammad Satari ◽  
Parviz Abdolmaleki ◽  
Saman Hosseinkhani

Non-viral gene carriers because of their limited side effects, biocompatibility, simplicity and taking the advantages of electrostatic interactions have shown noticeable potential in gene delivery. The low transfection rate of non-viral vectors under physiological conditions is a significant issue. Here, the aim of this study was to investigate the efficacy of hydrophilic and hydrophobic groups on gene carriers such as two synthesized amphiphilic polymer of dextran-stearic acid-spermine (DSASP) with verified lipid and amine conjugations that associated with Fe3O4 superparamagnetic nanoparticles to promote the target delivery and decrease the transfection time using static magnetic field. Our findings illustrate that magnetic nanoparticles are spherical with positive surface charges and superparamagnetic behaviors. The DSASP–pDNA/MNPs offered a strong pDNA condensation, protection against DNase degradation, significant cell viability in HEK 293T cells and. Although conjugations of spermine play a critical role in transfection efficiency, amphiphilic polymer with more derivatives of stearic acid showed better transfection yields. Therefore, DSASP amphiphilic magnetic carriers offer new insights for gene delivery due to the amine contents and ameliorate the uptake of complexes via cell membrane based on its hydrophilic surface.

2021 ◽  
Author(s):  
Mehrnoosh Kazemi Ashtiyani ◽  
Behnam Hajipour-Verdom ◽  
Mohammad Satari ◽  
Parviz Abdolmaleki ◽  
Saman Hosseinkhani ◽  
...  

Abstract BackgroundNon-viral gene carriers because of their limited side effects, biocompatibility, simplicity and taking the advantages of electrostatic interactions have shown noticeable potential in gene delivery. The low transfection rate of non-viral vectors under physiological conditions is a significant issue. MethodsWe investigated the efficacy of hydrophilic and hydrophobic groups on gene carriers such as two synthesized amphiphilic polymer of dextran-stearic acid-spermine (DSASP) with verified lipid and amine conjugations that associated with Fe3O4 superparamagnetic nanoparticles to promote the target delivery and decrease the transfection time using static magnetic field.ResultsOur findings illustrate that magnetic nanoparticles are spherical with positive surface charges and superparamagnetic behaviors. The DSASP–pDNA/MNPs offered a strong pDNA condensation, protection against DNase degradation, significant cell viability in HEK 293T cells. Although conjugations of spermine play a critical role in transfection efficiency, amphiphilic polymer with more derivatives of stearic acid showed better transfection yields. ConclusionDSASP amphiphilic magnetic carriers offer new insights for gene delivery due to the amine contents and ameliorate the uptake of complexes via cell membrane based on its hydrophilic surface.


Author(s):  
OLUWASEUN TAOFEEK

The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) responsible for the 2019 coronavirus disease (COVID-19) has caused a global health challenge. The SARS-COV-2 main protease, 3CLpro/Mpro plays a critical role in the viral gene expression and replication and has been a major target for inhibiting viral maturation and enhancing host innate immune responses against COVID-19. In this study, we screened a library of 38 phytochemicals from Nigella sativa (blackseed), Trigonella foenum-graecum (Fenugreek) and Anona muricata (Soursop) potent medicinal plants with reported antiviral properties - in a molecular docking protocol on 3CLpro using Autodock4.0 tool implanted in PyRx followed by docking validation and insilico absorption, distribution, metabolism, excretion, and toxicology (ADMET) evaluations. The docking results were visualized using Accelrys Discovery Studio and Pymol software. Among the 38 ligands screened, 19 showed significant interaction through non-covalent hydrogen bonding, hydrophobic, and electrostatic interactions with binding affinities from -5.3kcal/mol to -8.1kcal/mol indicating significant binding interactions at the active site binding pocket. Another important interaction observed in the study which mostly involve the transfer of charges was pi-interactions such as Pi-Pi interaction, Pi-Alkyl interaction, Pi-Sulfur interaction, Pi- Sigma, and Pi-Pi stacking. The docking results revealed that phytochemicals from T. foenum-graecum showed more 3CLpro inhibitory potential compared to those from N. sativa and A. muricata. Insilico ADMET evaluations for drug-like and lead-like characteristics however demonstrated that only 8 ligands - apigenin, kaempferol, luteolin, dithymoquinone, naringenine, nornuciferine, quercetin and nigellidine were actually drug-like; showed best activities against 3CLpro, and lack hepatotoxicity effects while none was lead-like. Insilico results of this study further suggested that drug repurposing candidates, remdesivir, indinavir,hydroxychloroquine, chloroquine and ritonavir,exhibited various interactions with 3CLpro. Hence, further in vitro and in vivo studies are proposed.


2021 ◽  
Author(s):  
Donghang Xu ◽  
Yuanqin Su ◽  
Qianhao Xu ◽  
Ting Huang ◽  
Zhilan Chen ◽  
...  

Abstract Cationic polyethylenimine (PEI) is regarded as the “golden standard” of non-viral gene vectors. However, the superiority of PEI with high positive charge density also induces its major drawback of cytotoxicity, which restricts its application for an effective and safe gene delivery to stem cells. To redress this shortcoming, herein, a magnetic gene complex containing uniform iron oxide nanoparticles (UIONPs), plasmid DNA, and free PEI is prepared through electrostatic interactions for the gene delivery to bone marrow-derived mesenchymal stem cells (BM-MSCs). Results show that UIONPs dramatically promote the gene delivery to BM-MSCs using the assistance of magnetic force. In addition, decreasing the free PEI nitrogen to DNA phosphate (N/P) ratio from 10 to 6 has little adverse impact on the transgene expression levels (over 300 times than that of PEI alone at the N/P ratio of 6) and significantly reduces the cytotoxicity to BM-MSCs. Further investigations confirmed that the decrease of free PEI has little influence on the cellular uptake after applying external magnetic forces, but that the reduced positive charge density decreases the cytotoxicity. The present study demonstrates that the magnetic gene delivery not only contributes to the enhanced gene delivery efficiency but also helps to reduce required amount of PEI, providing a potential strategy for an efficient and safe gene delivery to stem cells.


RSC Advances ◽  
2015 ◽  
Vol 5 (93) ◽  
pp. 76464-76471 ◽  
Author(s):  
Alejandro Méndez-Ardoy ◽  
Alejandro Díaz-Moscoso ◽  
Carmen Ortiz Mellet ◽  
Christophe Di Giorgio ◽  
Pierre Vierling ◽  
...  

Polycationic amphiphilic cyclodextrins (paCDs) have been shown to behave as efficient non-viral gene carriers paralleling the efficacy of commercial vectors towards a variety of cell lines.


2020 ◽  
Vol 20 ◽  
Author(s):  
L. Hajba ◽  
A. Guttman

: Adeno-associated virus (AAV) is one of the most promising viral gene delivery vectors with long-term gene expression and disease correction featuring high efficiency and excellent safety in human clinical trials. During the production of AAV vectors,there are several quality control (QC)parameters that should be rigorously monitored to comply with clini-cal safety and efficacy. This review gives a short summary of the most frequently used AVV production and purification methods,focusing on the analytical techniques applied to determine the full/empty capsid ratio and the integrity of the encapsidated therapeutic DNA of the products.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ji-wook Kim ◽  
Jie Wang ◽  
Hyungsub Kim ◽  
Seongtae Bae

AbstractMagnetic dipole coupling between the colloidal superparamagnetic nanoparticles (SPNPs) depending on the concentration has been paid significant attention due to its critical role in characterizing the Specific Loss Power (SLP) in magnetic nanofluid hyperthermia (MNFH). However, despite immense efforts, the physical mechanism of concentration-dependent SLP change behavior is still poorly understood and some contradictory results have been recently reported. Here, we first report that the SLP of SPNP MNFH agent shows strong concentration-dependent oscillation behavior. According to the experimentally and theoretically analyzed results, the energy competition among the magnetic dipole interaction energy, magnetic potential energy, and exchange energy, was revealed as the main physical reason for the oscillation behavior. Empirically demonstrated new finding and physically established model on the concentration-dependent SLP oscillation behavior is expected to provide biomedically crucial information in determining the critical dose of an agent for clinically safe and highly efficient MNFH in cancer clinics.


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