Diglycidyl Esters Cross-Linked with Low Molecular Weight Polyethyleneimine for Magnetofection

2015 ◽  
Vol 68 (10) ◽  
pp. 1535 ◽  
Author(s):  
Hao Yu ◽  
Shufeng Li ◽  
Liandong Feng ◽  
Yucheng Liu ◽  
Xiaoliang Qi ◽  
...  
Keyword(s):  
Electrostatic Interactions ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Repeat Unit ◽  
A549 Cells ◽  
Hydroxyl Groups ◽  
Cationic Polymers ◽  
Enhance Gene Expression ◽  
Low Cytotoxicity

Magnetic polyethyleneimine (PEI) complexes have demonstrated to be simple and efficient vectors for enhancing gene transfection. However, the high cytotoxicity of PEI restricts its further application in vivo. In this study, we synthesized several low cytotoxicity biodegradable cationic polymers derived from PEI (Mw 600) linked with diglycidyl tartrate (DT-PEI) or its analogues (diglycidyl succinate (DS-PEI) and diglycidyl malate (DM-PEI); D-PEIs for all 3 polymers). Moreover, a type of biocompatible magnetic nanoparticles (MNPs) with negative charges was prepared to assemble with D-PEIs/DNA complexes via electrostatic interactions. The magnetic ternary complexes have appropriate sizes of 120–150 nm and zeta potential values of ~20–25 mV. The transfection ability and cell viability of D-PEIs increased as the amount of hydroxyl groups increased in the repeat unit, which indicated that increasing the hydroxyl number in the backbone of D-PEIs can enhance gene expression and decrease cytotoxicity in A549 cells. Magnetofection of DT-PEI showed similar transfection efficiency with 30 min incubation; in contrast, the standard incubation time was 4 h. All three magnetic complexes displayed lower cytotoxicity when compared with those of PEI complexes in COS-7 and A549. These results indicated that these series of magnetic PEI derivatives complexes could be potential nanocarriers for gene delivery.

Efficient gene transfection to liver cells via the cellular regulation of a multifunctional polylactitol-based gene transporter

2016 ◽  
Vol 4 (12) ◽  
pp. 2208-2218 ◽  
Author(s):  
Young-Dong Kim ◽  
Tae-Eun Park ◽  
Bijay Singh ◽  
Kye-Soo Cho ◽  
Jaiprakash N. Sangshetti ◽  
...  
Keyword(s):  
Liver Cell ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Gene Carrier ◽  
Cell Targeting ◽  
Cellular Regulation ◽  
Efficient Gene ◽  
Low Cytotoxicity

A new polylactitol-based multifunctional gene carrier has shown low cytotoxicity, a high transfection efficiency, and liver cell targeting bothin vitroandin vivo.

scholarly journals Chondroitin Sulfate Capsule System for Efficient and Secure Gene Delivery

2010 ◽  
Vol 13 (3) ◽  
pp. 351 ◽  
Author(s):  
Tomoaki Kurosaki ◽  
Takashi Kitahara ◽  
Shintaro Fumoto ◽  
Koyo Nishida ◽  
Kayo Yamamoto ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Chondroitin Sulfate ◽  
Transfection Efficiency ◽  
Animal Experiments ◽  
Ternary Complexes ◽  
Trimethylammonium Chloride ◽  
Cationic Polymers ◽  
Low Cytotoxicity

Purpose. In this study, we developed various ternary complexes of encapsulated polyplexes and lipoplexes using chondroitin sulfate (CS) and investigated their universal usefulness for gene delivery. Methods. To prepare the cationic complexes, pDNA was mixed with some cationic vectors such as poly-L-arginine, poly-L-lysine, N-[1-(2, 3-dioleyloxy) propyl]-N, N, N-trimethylammonium chloride (DOTMA)-cholesterol liposomes, and DOTMA- dioleylphosphatidylethanolamine (DOPE) liposomes. CS was added to the cationic complexes for constructions of ternary complexes. We examined in vitro transfection efficiency, cytotoxicity, hematotoxicity, and in vivo transfection efficiency of the ternary complexes. Result. The cationic polymers and cationic liposomes bound to pDNA and formed stable cationic polyplexes and lipoplexes, respectively. Those cationic complexes showed high transgene efficiency in B16-F10 cells; however, they also had high cytotoxicity and strong agglutination with erythrocytes. CS could encapsulate the polyplexes and lipoplexes and form stable anionic particles without disrupting their structures. The ternary complexes encapsulated by CS showed high transgene efficiency in B16-F10 cells with low cytotoxicity and agglutination. As the result of animal experiments, the polyplexes had little transgene efficiency after intravenous administration in mice, whereas polyplexes encapsulated by CS showed specifically high transgene efficiency in the spleen. The capsulation of CS, however, reduced the high transgene efficiency of the lipoplexes. Conclusion. These results indicate that CS can contribute to polyplex-mediated gene delivery systems for effective and safe gene therapy.

Non-Viral Vectors for Gene Delivery

2018 ◽  
Vol 9 (1) ◽  
pp. 4-11 ◽  
Author(s):  
Aparna Bansal ◽  
Himanshu
Keyword(s):  
Gene Therapy ◽  
Viral Vectors ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Expression System ◽  
Target Cells ◽  
Specific Expression ◽  
Naked Dna

Introduction: Gene therapy has emerged out as a promising therapeutic pave for the treatment of genetic and acquired diseases. Gene transfection into target cells using naked DNA is a simple and safe approach which has been further improved by combining vectors or gene carriers. Both viral and non-viral approaches have achieved a milestone to establish this technique, but non-viral approaches have attained a significant attention because of their favourable properties like less immunotoxicity and biosafety, easy to produce with versatile surface modifications, etc. Literature is rich in evidences which revealed that undoubtedly, non–viral vectors have acquired a unique place in gene therapy but still there are number of challenges which are to be overcome to increase their effectiveness and prove them ideal gene vectors. Conclusion: To date, tissue specific expression, long lasting gene expression system, enhanced gene transfection efficiency has been achieved with improvement in delivery methods using non-viral vectors. This review mainly summarizes the various physical and chemical methods for gene transfer in vitro and in vivo.

Retracted Article: A multifunctional self-dissociative polyethyleneimine derivative coating polymer for enhancing the gene transfection efficiency of DNA/polyethyleneimine polyplexes in vitro and in vivo

2015 ◽  
Vol 6 (5) ◽  
pp. 780-796 ◽  
Author(s):  
Cheng Wang ◽  
Xiuli Bao ◽  
Xuefang Ding ◽  
Yang Ding ◽  
Sarra Abbad ◽  
...  
Keyword(s):  
Transfection Efficiency ◽  
Gene Transfection ◽  
Retracted Article ◽  
First Time

A novel coating polymer LPHF is developed for the first time to elevate the transfection efficiency of DP binary polyplexes in vitro and in vivo.

Evaluation of low molecular weight polyethylenimine-introduced chitosan for gene delivery to mesenchymal stem cells

2020 ◽  
Vol 10 (7) ◽  
pp. 1170-1176
Author(s):  
Minchen Liu ◽  
Yulan Hu ◽  
Yi Feng
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Gene Delivery ◽  
Transfection Efficiency ◽  
A549 Cells ◽  
Safety Evaluation ◽  
Physicochemical Characteristics ◽  
Hatching Rate

This study aimed to examine the transfection ability of polyethylenimine (PEI) (1800 Da)-grafted chitosan (10 kDa) (CP), a newly synthesized PEI derivative, in mesenchymal stem cells (MSCs). The safety evaluation of the complex/DNA was studied in vitro and in vivo. In addition, CP/pGL3 was applied to investigate the effects of transfection efficiency. In this study, CP/DNA can be formed with compatible physicochemical characteristics for gene delivery. CP cytotoxicity decreased in A549 cells. Moreover, a zebrafish embryo model was used for evaluating the safety in vivo. Compared to the PEI (25 kDa) group, the zebrafish hatching rate increased and the mortality rate decreased in the CP/DNA group, which provided an indication of the safety of CP. In comparison with chitosan (100 kDa)-PEI (1200 Da), CP's transfection efficiency was higher in both A549 cells and MSCs. This study aimed to lay the foundation for further applications of CP in gene delivery. Therefore, further gene therapy investigations of CP by using MSCs need to be performed.

In vitro and in vivo gene transfection using biodegradable and low cytotoxic nanomicelles based on dendritic block copolymers

2015 ◽  
Vol 3 (4) ◽  
pp. 688-699 ◽  
Author(s):  
Yan Liu ◽  
Chao Lin ◽  
Jianbo Li ◽  
Yang Qu ◽  
Jie Ren
Keyword(s):  
Block Copolymers ◽  
Viral Vectors ◽  
Gene Transfection ◽  
Low Cytotoxicity

Dendritic PCL-b-PDMAEMA copolymers have been used as non-viral vectors for gene transfection and exhibited high transfection efficiencies and low cytotoxicity.

scholarly journals A Biodegradable Polyethylenimine-Based Vector Modified by Trifunctional Peptide R18 for Enhancing Gene Transfection Efficiency In Vivo

PLoS ONE ◽  
2016 ◽  
Vol 11 (12) ◽  
pp. e0166673 ◽  
Author(s):  
Jing Hu ◽  
Manman Zhu ◽  
Kehai Liu ◽  
Hua Fan ◽  
Wenfang Zhao ◽  
...  
Keyword(s):  
Transfection Efficiency ◽  
Gene Transfection

Self-assembling Janus dendritic polymer for gene delivery with low cytotoxicity and high gene transfection efficiency

2016 ◽  
Vol 4 (39) ◽  
pp. 6462-6467 ◽  
Author(s):  
Sheng-Gang Ding ◽  
Lei Yu ◽  
Long-Hai Wang ◽  
Lin-Ding Wang ◽  
Zhi-Qiang Yu ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Dendritic Polymer ◽  
Self Assembling ◽  
High Gene ◽  
Low Cytotoxicity

Polycations have high DNA condensing ability, low immunogenicity, and great adaptability, which make them promising for gene delivery.

scholarly journals Dual delivery of nucleic acids and PEGylated-bisphosphonates via calcium phosphate nanoparticles

2019 ◽  
Author(s):  
Sofia Bisso ◽  
Simona Mura ◽  
Bastien Castagner ◽  
Patrick Couvreur ◽  
Jean-Christophe Leroux
Keyword(s):  
Calcium Phosphate ◽  
Plasmid Dna ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Physical Stability ◽  
Entrapment Efficiency ◽  
Endosomal Escape ◽  
Particle Uptake ◽  
Success Stories

AbstractDespite many years of research and a few success stories with gene therapeutics, efficient and safe DNA delivery remains a major bottleneck for the clinical translation of gene-based therapies. Gene transfection with calcium phosphate (CaP) nanoparticles brings the advantages of low toxicity, high DNA entrapment efficiency and good endosomal escape properties. The macroscale aggregation of CaP nanoparticles can be easily prevented through surface coating with bisphosphonate conjugates. Bisphosphonates, such as alendronate, recently showed promising anticancer effects. However, their poor cellular permeability and preferential bone accumulation hamper their full application in chemotherapy. Here, we investigated the dual delivery of plasmid DNA and alendronate using CaP nanoparticles, with the goal to facilitate cellular internalization of both compounds and potentially achieve a combined pharmacological effect on the same or different cell lines. A pH-sensitive poly(ethylene glycol)-alendronate conjugate was synthetized and used to formulate stable plasmid DNA-loaded CaP nanoparticles. These particles displayed good transfection efficiency in cancer cells and a strong cytotoxic effect on macrophages. The in vivo transfection efficiency, however, remained low, calling for an improvement of the system, possibly with respect to the extent of particle uptake and their physical stability.Graphical abstract

scholarly journals Gene-Activated Matrix with Self-Assembly Anionic Nano-Device Containing Plasmid DNAs for Rat Cranial Bone Augmentation

Materials ◽  
2021 ◽  
Vol 14 (22) ◽  
pp. 7097
Author(s):  
Masahito Hara ◽  
Yoshinori Sumita ◽  
Yukinobu Kodama ◽  
Mayumi Iwatake ◽  
Hideyuki Yamamoto ◽  
...  
Keyword(s):  
Self Assembly ◽  
Electrostatic Interactions ◽  
Cranial Bone ◽  
Bone Augmentation ◽  
Mesenchymal Progenitor Cells ◽  
Anionic Polymer ◽  
Morphogenetic Protein ◽  
Low Cytotoxicity

We have developed nanoballs, a biocompatible self-assembly nano-vector based on electrostatic interactions that arrange anionic macromolecules to polymeric nanomaterials to create nucleic acid carriers. Nanoballs exhibit low cytotoxicity and high transfection efficiently in vivo. This study investigated whether a gene-activated matrix (GAM) composed of nanoballs containing plasmid (p) DNAs encoding bone morphogenetic protein 4 (pBMP4) could promote bone augmentation with a small amount of DNA compared to that composed of naked pDNAs. We prepared nanoballs (BMP4-nanoballs) constructed with pBMP4 and dendrigraft poly-L-lysine (DGL, a cationic polymer) coated by γ-polyglutamic acid (γ-PGA; an anionic polymer), and determined their biological functions in vitro and in vivo. Next, GAMs were manufactured by mixing nanoballs with 2% atelocollagen and β-tricalcium phosphate (β-TCP) granules and lyophilizing them for bone augmentation. The GAMs were then transplanted to rat cranial bone surfaces under the periosteum. From the initial stage, infiltrated macrophages and mesenchymal progenitor cells took up the nanoballs, and their anti-inflammatory and osteoblastic differentiations were promoted over time. Subsequently, bone augmentation was clearly recognized for up to 8 weeks in transplanted GAMs containing BMP4-nanoballs. Notably, only 1 μg of BMP4-nanoballs induced a sufficient volume of new bone, while 1000 μg of naked pDNAs were required to induce the same level of bone augmentation. These data suggest that applying this anionic vector to the appropriate matrices can facilitate GAM-based bone engineering.

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