11 results on '"Oskuee, Reza Kazemi"'
Search Results
2. Synthesis and evaluation of gene delivery vectors based on PEImodified metal-organic framework (MOF) nanoparticles.
- Author
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Khosrojerdi, Somayeh, Gholami, Leila, Khazaei, Majid, Hashemzadeh, Alireza, Darroudi, Majid, and Oskuee, Reza Kazemi
- Subjects
METAL-organic frameworks ,NANOPARTICLES ,CYTOTOXINS ,ZETA potential ,POLYETHYLENEIMINE - Abstract
Objective(s): Zirconium-based metal-organic frameworks (MOFs) nanostructures, due to their capability of easy surface modification, are considered interesting structures for delivery. In the present study, the surfaces of UIO-66 and NH2-UIO-66 MOFs were modified by polyethyleneimine (PEI) 10000 Da, and their efficiency for plasmid delivery was evaluated. Materials and Methods: Two different approaches, were employed to prepare surface-modified nanoparticles. The physicochemical characteristics of the resulting nanoparticles, as well as their transfection efficiency and cytotoxicity, were investigated on the A549 cell line. Results: The sizes of DNA/nanocarriers for PEI-modified UIO-66 (PEI-UIO-66) were between 212-291 nm and 267-321 nm for PEI 6-bromohexanoic acid linked UIO-66 (PEI-HEX-UIO-66). The zeta potential of all was positive with the ranges of +16 to +20 mV and +23 to +26 mV for PEI-UIO-66 and PEI-HEX-UIO-66, respectively. Cellular assay results showed that the PEI linking method had a higher rate of gene transfection efficiency with minimal cytotoxicity than the wet impregnation method. The difference between transfection of modified nanoparticles compared to the PEI 10 kDa was not significant but the PEI-HEX-UIO-66 showed less cytotoxicity. Conclusion: The present study suggested that the post-synthetic modification of MOFs with PEI 10000 Da through EDC/NHS+6-bromohexanoic acid reaction can be considered as an effective approach for modifying MOFs' structure in order to obtain nanoparticles with better biological function in the gene delivery process. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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3. Brevinin-2R-linked polyethylenimine as a promising hybrid nanogene-delivery vector.
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Zohrab, Fatemeh, Asoodeh, Ahmad, Jalili, Amin, Darroudi, Majid, and Oskuee, Reza Kazemi
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GREEN fluorescent protein ,REPORTER genes ,ZETA potential ,POLYETHYLENEIMINE ,CELL lines - Abstract
Objective(s): Polyethylenimine (PEI) is one of the most widely used polymers in gene delivery. The aim of this study was to modify PEI by replacing some of its primary amines with Brevinin 2R (BR-2R) peptide in order to increase the efficiency of gene delivery. Materials and Methods: Polyethylenimine was modified by BR-2R peptide by two different approaches; A) conjugation methods including (І) using succinimidyl 3-(2-pyridyldithio) propionate (SPDP), (П) EDC/NHS protocol and (ПІ) EDC/NHS+6-bromohexanoic acid protocol, and B) physical interaction method. The modified polymers were characterized for their ability of plasmid condensation, number of primary amines, size and zeta potential. The transfection efficiency and cytotoxicity were evaluated on HEK293, L929, WEHI164 and Neuro2A cell lines by green fluorescent protein (GFP)-based plasmid (pGFP) reporter gene and viability assays, respectively. Apoptosis induction ability was also evaluated via PI/Annexin V assay. Results: Polyplex had size and zeta potential between 200-270 nm and +21.5- +28.4 mV, respectively. All vectors were able to condense plasmid DNA in C/P=4 (carrier-plasmid ratio). Transfection results on the Neuro2A cell line showed that the vector containing the BR-2R peptide, which was synthesized using EDC-NHS protocol had the best transfection efficiency. Conclusion: Our results showed that conjugation of Brevinin 2R as cell penetrating peptide to polyethyleneimine could enhance the transfection ability of the polymer. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
4. Progress in the development of lipopolyplexes as efficient non-viral gene delivery systems.
- Author
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Rezaee, Mehdi, Oskuee, Reza Kazemi, Nassirli, Hooriyeh, and Malaekeh-Nikouei, Bizhan
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LIPOSOMES , *SMALL interfering RNA , *GENE delivery techniques , *DRUG delivery systems , *NUCLEIC acids , *THERAPEUTICS - Abstract
Efficient gene therapy is mainly dependent on the gene transfer capability of gene delivery vectors. Non-viral vectors have become the research interest of many researchers because these vectors are safer than viral vectors. Acquiring the advantages of both polyplexes and lipoplexes, the lipopolyplex (LPP) is a ternary nanocomplex composed of cationic liposome, polycation, and nucleic acid. Considering the polycationic component, ternary complexes (LPPs) are divided into cationic polymer-based LPPs and cationic peptide-based LPPs. Considering the capability of rational design, LPP is an interesting field of research to design a more potent nucleic acid carrier. With the promising transfection activity and safety observed in the LPPs, many researchers have formulated various types of lipids and polycations to achieve an efficient and safe carrier for gene therapy. Here we provide a review on the designed LPPs for efficient delivery of different nucleic acids such as plasmid DNA, siRNA, shRNA, and DNA vaccines. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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5. Preparation, characterization and transfection efficiency of nanoparticles composed of alkane-modified polyallylamine.
- Author
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Oskuee, Reza Kazemi, Zakeri, Vahideh, Gholami, Leila, and Malaekeh-Nikouei, Bizhan
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NANOPARTICLES , *ALLYLAMINES , *GENETIC transformation , *NANOSTRUCTURED materials , *DNA - Abstract
Objective(s): Although viral vectors are considered efficient gene transfer agents, their board application has been limited by toxicity, immunogenicity, mutagenicity and small gene carrying capacity. Non-viral vectors are safe but they suffer from low transfection efficiency. In the present study, polyallylamine (PAA) in two molecular weights (15 and 65 kDa) was modified by alkane derivatives in order to increase transfection activity and to decrease cytotoxicity. Materials and Methods: Modified PAA was synthesized using three alkane derivatives (1-bromobutane, 1-bromohexane and 1-bromodecane) in different grafting percentages (10, 30 and 50). The condensation ability of modified PAA was determined by ethidium bromide test. The prepared polyplexes, complexes of modified PAA and DNA, were characterized by size and zeta potential. Transfection activity of polyplexes was checked in Neuro2A cells. The cytotoxicity of vector was examined in the same cell line. Results: DNA condensation ability of PAA was decreased after modification but modified polymer could still condense DNA at moderate and high carrier to plasmid (C/P) ratios. Most of polyplexes composed of modified polymer had mean size less than 350 nm. They showed a positive zeta potential, but some vectors with high percentage of grafting had negative surface charge. Transfection efficiency was increased by modification of PAA by 1-bromodecane in grafting percentages of 30 and 50%. Modification of polymer reduced polymer cytotoxicity especially in C/P ratio of 2. Conclusion: Results of the present study indicated that modification of PAA with alkane derivatives can help to prepare gene carriers with better transfection activity and less cytotoxicity. [ABSTRACT FROM AUTHOR]
- Published
- 2015
6. A simple approach for producing highly efficient DNA carriers with reduced toxicity based on modified polyallylamine.
- Author
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Oskuee, Reza Kazemi, Dosti, Fatemeh, Gholami, Leila, and Malaekeh-Nikouei, Bizhan
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DNA , *AMINES , *GENE delivery techniques , *GENE transfection , *HYDROPHOBIC interactions , *MOLECULAR weights , *BROMIDES - Abstract
Nowadays gene delivery is a topic in many research studies. Non-viral vectors have many advantages over viral vectors in terms of safety, immunogenicity and gene carrying capacity but they suffer from low transfection efficiency and high toxicity. In this study, polyallylamine (PAA), the cationic polymer, has been modified with hydrophobic branches to increase the transfection efficiency of the polymer. Polyallylamine with molecular weights of 15 and 65 kDa was selected and grafted with butyl, hexyl and decyl acrylate at percentages of 10, 30 and 50. The ability of the modified polymer to condense DNA was examined by ethidium bromide test. The complex of modified polymer and DNA (polyplex) was characterized for size, zeta potential, transfection efficiency and cytotoxicity in Neuro2A cell lines. The results of ethidium bromide test showed that grafting of PAA decreased its ability for DNA condensation but vectors could still condense DNA at moderate and high carrier to DNA ratios. Most of polyplexes had particle size between 150 and 250 nm. The prepared vectors mainly showed positive zeta potential but carriers composed of PAA with high percentage of grafting had negative zeta potential. The best transfection activity was observed in vectors with hexyl acrylate chain. Grafting of polymer reduced its cytotoxicity especially at percentages of 30 and 50. The vectors based of PAA 15 kDa had better transfection efficiency than the vectors made of PAA 65 kDa. In conclusion, results of the present study indicated that grafting PAA 15 kDa with high percentages of hexyl acrylate can help to prepare vectors with better transfection efficiency and less cytotoxicity. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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7. Reverse relation between cytotoxicity and Polyethylenimine/DNA ratio, the effect of using HEPES-buffered saline (HBS) medium in gene delivery.
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Dabbaghi, Maryam, Hashemi, Khadijeh, Oskuee, Reza Kazemi, and Afkhami-Goli, Amir
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POLYETHYLENEIMINE , *UNFOLDED protein response , *CATIONIC polymers , *DNA , *GENES - Abstract
Polyethyleneimine (PEI) is considered a promising cationic polymer in non-viral gene delivery. DNA binding properties and other biochemical characteristics of PEI such as the proton sponge phenomenon, offered the branched 25 kDa PEI to be widely used for therapeutic DNA delivery, although the possible cytotoxic effects and the best conditions of PEI preparation are not still well recognized. While higher PEI/Plasmid ratios have increased transfection efficiencies, it induces more cell stress and toxicity. Considering that the PEI particle size and resulting cytotoxicity are affected by media ions, we used Neuro2A cells to assess the cell stress properties of PEI/Plasmid complexes prepared in a HEPES-buffered saline medium. Delivery of a plasmid containing EGFP happened in all increasing ratios of PEI/plasmid from 0.5, 2, 4, and 6, while higher ratios induced less unfolded protein response as evidenced by lower transcription of ER stress markers Grp78, Atf4, Chop , Xbp1 , and induced Xbp1 splicing. These data were also supported by MTT cytotoxicity assay results. These findings indicate that preparing higher PEI/plasmid ratio complexes (using the equivalent of 200 ng DNA) in the HBS medium leads to less cytotoxicity. [Display omitted] • All the increasing ratios of PEI/plasmid have transfection capabilities. • Higher ratios of PEI/plasmid induced lower transcription of ER stress markers. • HBS medium is preferable to minimize toxic effects in gene therapies. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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8. PAMAM-pullulan conjugates as targeted gene carriers for liver cell.
- Author
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Askarian, Saeedeh, Abnous, Khalil, Ayatollahi, Sara, Farzad, Sara Amel, Oskuee, Reza Kazemi, and Ramezani, Mohammad
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LIVER cells , *NUCLEIC acids , *GENE transfection , *CELL-mediated cytotoxicity , *GLYCOPROTEINS - Abstract
Targeted nano-carriers are highly needed to promote nucleic acid delivery into the specific cell for therapeutic approaches. Pullulan as a linear carbohydrate has an intrinsic liver targeting property interacting with asialoglycoprotein receptor (ASGPR) found on liver cells. In the present study, we developed polyamidoamine (PAMAM)-pullulan conjugates and investigated their targeting activity in delivering gene into liver cells. The particle size, zeta potential, buffering capacity and ethidium bromide exclusion assays of the conjugates were evaluated. The cytotoxicity and transfection efficiency of new derivatives were assessed following in vitro transfection of HepG2 (receptor positive) and N2A (receptor negative) cell lines. Size of conjugated polymers ranged between 118 and 184 nanometers and their cytotoxicity were similar to PAMAM. Among six produced nanocarriers, G4PU4 and G5PU4 enhanced transfection efficiency in HepG2 cells compared to unmodified PAMAM. Therefore, the PAMAM-pullulan derivatives seem to improve delivery of nucleic acids into the liver cells expressing asialoglycoprotein receptor with minimal transfection in non-targeted cells. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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9. Gene delivery to neuroblastoma cells by poly (l-lysine)-grafted low molecular weight polyethylenimine copolymers.
- Author
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Askarian, Saeedeh, Abnous, Khalil, Darroudi, Majid, Oskuee, Reza Kazemi, and Ramezani, Mohammad
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NEUROBLASTOMA , *COPOLYMERS , *CANCER cells , *GENETIC carriers , *ZETA potential , *MOLECULAR weights , *DNA condensation , *GENE delivery techniques - Abstract
Polyethylenimine (PEI) and poly ( l -lysine) (PLL) are among the most investigated non-viral gene carriers. However, both polymers contain deficiencies that restrict their applications. In the present study, we synthesized PLL-alkyl-PEI conjugates via 6-carbon alkyl linker and investigated their possible advantages in gene delivery. Four PLL copolymers were synthesized with different molecular weights and ratios of PEI. The physiochemical properties of synthesized conjugates such as size, zeta potential, DNA condensation ability, buffering capacity and cytotoxicity were investigated. Renilla luciferase assay was employed to evaluate the gene transfection efficiency of pDNA-polymer to Neuro2A cell line. DNA condensation and particle size measurements showed that new PLL-PEI conjugates could form polyplexes in nano-scale size in the range of 99–122 nm and were able to condense DNA at low concentration. While cytotoxicity reduced in some groups, the transfection efficiency increased about 2.8 and 4 fold as compared to the unmodified PEI 1.8 kDa and 10 kDa, respectively. The results of the present study showed that the chemical modifications of PEI with PLL could significantly improve transfection efficiency and PLP10-10% shows the most promise as a new gene carrier. [ABSTRACT FROM AUTHOR]
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- 2016
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10. Cellular delivery of shRNA using aptamer-conjugated PLL-alkyl-PEI nanoparticles.
- Author
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Askarian, Saeedeh, Abnous, Khalil, Taghavi, Sahar, Oskuee, Reza Kazemi, and Ramezani, Mohammad
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LUNG cancer treatment , *CELL-mediated cytotoxicity , *RNA , *APTAMERS , *GENE delivery techniques , *SURFACE charges - Abstract
Introduction of an efficient gene delivery vector is still the main challenge of gene therapy. Both polyethylenimine (PEI) and poly( l -lysine) (PLL) comprise disadvantages which limited their application. To explore whether their deficiencies could be compensated by preparing copolymers consisting of both PLL and PEI, we generated several combinations of PLL-alkyl-PEI copolymers conjugated to aptamer and evaluated their both gene delivery efficiency and down-regulation of Bcl-XL, an anti-apoptotic gene, in lung cancer cell line. PLL was conjugated to either 10% or 50% of PEI by grafting different percentages of PEI to alkylated-PLL as core. The properties of modified polymers including size, surface charge density, DNA condensation ability, buffering capacity and cytotoxicity were evaluated. According to transfection results, aptamer conjugated PLL-alkyl-10%-PEI (PLPE8%) was selected for further gene silencing study by plasmid shRNA. Decrease in Bcl-XL gene expression was estimated by both RT-PCR and western-blot experiments. The obtained results revealed that the new copolymers had appropriate nano-scale size (117–128 nm) even after aptamer conjugation (168–183 nm). Moreover, they exhibited increased transfection efficiencies by up to 1.8–5 folds and acceptable cytotoxicity. The apoptosis was induced in transfected cells by shRNA-aptamer-copolymer due to the down-regulation of mRNA and protein levels. This study suggested a new vector for targeted non-viral gene delivery with high transfection efficiency in lung cancer or pulmonary systems. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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11. Self-assembly of an aptamer-decorated chimeric peptide nanocarrier for targeted cancer gene delivery.
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Dehghani, Sadegh, Alibolandi, Mona, Tehranizadeh, Zeinab Amiri, Oskuee, Reza Kazemi, Nosrati, Rahim, Soltani, Fatemeh, and Ramezani, Mohammad
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CANCER genes , *GENE delivery techniques , *GENE transfection , *APTAMERS , *MOLECULAR weights , *TANDEM repeats , *NUCLEAR DNA , *NUCLEOLIN - Abstract
[Display omitted] • KALA-LMWP-NLS chimeric peptide (KLN) was designed and expressed in E. coli Bl21. • KLN/pDNA/Aptamer nanoparticles were synthesized using electrostatic self-assembly. • Functionality of each segment in the vector structure was evaluated. • Synthesized nanoparticles significantly protected plasmid against serum nucleases. • Nanoparticles showed remarkable transfection efficiency and low cytotoxicity. In this study, we developed a peptide-based non-viral carrier decorated with aptamer to overcome the specific gene delivery barriers. The carrier (KLN/Apt) was designed to contain multiple functional segments, including 1) two tandem repeating units of low molecular weight protamine (LMWP) to condense DNA into stable nanosize particles and protect it from enzymatic digestion, 2) AS1411 aptamer as targeting moiety to target nucleolin and promote carrier internalization, 3) a synthetic pH-sensitive fusogenic peptide (KALA) for disrupting endosomal membranes and enhancing cytosol escape of the nanoparticles, and 4) a nuclear localization signal (NLS) for active cytoplasmic trafficking and nuclear delivery of DNA. The obtained results revealed the developed carrier capacity in terms of specific cell targeting, overcoming cellular gene delivery barriers, and mediating efficient gene transfection. The KLN/pDNA/aptamer nanoparticles offer remarkable potential for the conceptual design and formation of promising multi-functionalized carriers towards the most demanding therapeutic applications. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
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