scholarly journals Lignin-Based Nonviral Gene Carriers Functionalized by Poly[2-(Dimethylamino)ethyl Methacrylate]: Effect of Grafting Degree and Cationic Chain Length on Transfection Efficiency

Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 102
Author(s):  
Xiaohong Liu ◽  
Hui Yin ◽  
Xia Song ◽  
Zhongxing Zhang ◽  
Jun Li
Keyword(s):  
Gene Delivery ◽  
Chain Length ◽  
Cell Lines ◽  
Transfection Efficiency ◽  
Graft Copolymers ◽  
Gene Transfection ◽  
Structural Factors ◽  
Ethyl Methacrylate ◽  
Branched Structure ◽  
Grafting Degree

Lignin is a natural renewable biomass resource with great potential for applications, while its development into high value-added molecules or materials is rare. The development of biomass lignin as potential nonviral gene delivery carriers was initiated by our group through the “grafting-from” approach. Firstly, the lignin was modified into macroinitiator using 2-bromoisobutyryl bromide. Then cationic polymer chains of poly[2-(dimethylamino)ethyl methacrylate] (PDMAEMA) were grown from the lignin backbone using atom transfer radical polymerization (ATRP) to yield lignin-PDMAEMA graft copolymers (LPs) with branched structure. To gain a deep understanding of the relationship between the nonviral gene transfection efficiency of such copolymers and their structural and compositional factors, herein eight lignin-based macroinitiators with different modification degrees (MDs, from 3.0 to 100%) were synthesized. Initiated by them, a series of 20 LPs were synthesized with varied structural factors such as grafting degree (GD, which is equal to MD, determining the cationic chain number per lignin macromolecule), cationic chain length (represented by number of repeating DMAEMA units per grafted arm or degree of polymerization, DP) as well as the content of N element (N%) which is due to the grafted PDMAEMA chains and proportional to molecular weight of the LPs. The in vitro gene transfection capability of these graft copolymers was evaluated by luciferase assay in HeLa, COS7 and MDA-MB-231cell lines. Generally, the copolymers LP-12 (N% = 7.28, MD = 36.7%, DP = 13.6) and LP-14 (N% = 6.05, MD = 44.4%, DP = 5.5) showed good gene transfection capabilities in the cell lines tested. Overall, the performance of LP-12 was the best among all the LPs in the three cell lines at the N/P ratios from 10 to 30, which was usually several times higher than PEI standard. However, in MDA-MB-231 at N/P ratio of 30, LP-14 showed the best gene transfection performance among all the LPs. Its gene transfection efficiency was ca. 11 times higher than PEI standard at this N/P ratio. This work demonstrated that, although the content of N element (N%) which is due to the grafted PDMAEMA chains primarily determines the gene transfection efficiency of the LPs, it is not the only factor in explaining the performance of such copolymers with the branched structure. Structural factors of these copolymers such as grafting degree and cationic chain length could have a profound effect on the copolymer performance on gene transfection efficiency. Through carefully adjusting these factors, the gene transfection efficiency of the LPs could be modulated and optimized for different cell lines, which could make this new type of biomass-based biomaterial an attractive choice for various gene delivery applications.

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 Interaction kinetics of peptide lipids-mediated gene delivery

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Yinan Zhao ◽  
Tianyi Zhao ◽  
Yanyan Du ◽  
Yingnan Cao ◽  
Yang Xuan ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Endosomal Escape ◽  
Late Endosomes ◽  
Key Factor ◽  
Interaction Kinetics ◽  
Dna Release

Abstract Background During the course of gene transfection, the interaction kinetics between liposomes and DNA is speculated to play very important role for blood stability, cellular uptake, DNA release and finally transfection efficiency. Results As cationic peptide liposomes exhibited great gene transfer activities both in vitro and in vivo, two peptide lipids, containing a tri-ornithine head (LOrn3) and a mono-ornithine head (LOrn1), were chosen to further clarify the process of liposome-mediated gene delivery in this study. The results show that the electrostatically-driven binding between DNA and liposomes reached nearly 100% at equilibrium, and high affinity of LOrn3 to DNA led to fast binding rate between them. The binding process between LOrn3 and DNA conformed to the kinetics equation: y = 1.663631 × exp (− 0.003427x) + 6.278163. Compared to liposome LOrn1, the liposome LOrn3/DNA lipoplex exhibited a faster and more uniform uptake in HeLa cells, as LOrn3 with a tri-ornithine peptide headgroup had a stronger interaction with the negatively charged cell membrane than LOrn1. The efficient endosomal escape of DNA from LOrn3 lipoplex was facilitated by the acidity in late endosomes, resulting in broken carbamate bonds, as well as the “proton sponge effect” of the lipid. Conclusions The interaction kinetics is a key factor for DNA transfection efficiency. This work provided insights into peptide lipid-mediated DNA delivery that could guide the development of the next generation of delivery systems for gene therapeutics.

scholarly journals Combining Hyaluronic Acid with Chitosan Enhances Gene Delivery

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Ana V. Oliveira ◽  
Diogo B. Bitoque ◽  
Gabriela A. Silva
Keyword(s):  
Hyaluronic Acid ◽  
Gene Delivery ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Nonviral Vectors ◽  
Anionic Polymer ◽  
Dna Release

The low gene transfer efficiency of chitosan-DNA polyplexes is a consequence of their high stability and consequent slow DNA release. The incorporation of an anionic polymer is believed to loosen chitosan interactions with DNA and thus promote higher transfection efficiencies. In this work, several formulations of chitosan-DNA polyplexes incorporating hyaluronic acid were prepared and characterized for their gene transfection efficiency on both HEK293 and retinal pigment epithelial cells. The different polyplex formulations showed morphology, size, and charge compatible with a role in gene delivery. The incorporation of hyaluronic acid rendered the formulations less stable, as was the goal, but it did not affect the loading and protection of the DNA. Compared with chitosan alone, the transfection efficiency had a 4-fold improvement, which was attributed to the presence of hyaluronic acid. Overall, our hybrid chitosan-hyaluronic acid polyplexes showed a significant improvement of the efficiency of chitosan-based nonviral vectorsin vitro, suggesting that this strategy can further improve the transfection efficiency of nonviral vectors.

An acoustic field-based conformal transfection system for improving gene delivery efficiency

2021 ◽  
Author(s):  
Liting Xie ◽  
Jieqiong Wang ◽  
Shuai Zhao ◽  
Manlin Lai ◽  
Tian'an Jiang ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Acoustic Field ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
High Specificity ◽  
Low Toxicity ◽  
Delivery Efficiency

Ultrasound-activated microbubbles destruction is a promising platform for gene delivery due to the low toxicity, non-invasiveness, and high specificity. However, the gene transfection efficiency is still low, especially for suspension...

Fabrication of aminated poly(glycidyl methacrylate)-based polymers for co-delivery of anticancer drugs and the p53 gene

2020 ◽  
Vol 8 (41) ◽  
pp. 9555-9565 ◽  
Author(s):  
Lei Li ◽  
Hongrui Tian ◽  
Jinlin He ◽  
Mingzu Zhang ◽  
Zuguang Li ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Protein Aggregation ◽  
Anticancer Drugs ◽  
Glycidyl Methacrylate ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
P53 Gene

Aminated poly(glycidyl methacrylate)-based polymers for gene delivery not only can reduce toxicity and improve solubility, but can improve gene transfection efficiency and reduce protein aggregation.

Cationic Micelles Based on Polyhedral Oligomeric Silsesquioxanes for Enhanced Gene Transfection

2016 ◽  
Vol 69 (4) ◽  
pp. 363 ◽  
Author(s):  
Connie K. Liu ◽  
Qingqing Dou ◽  
Sing Shy Liow ◽  
Jatin N. Kumar ◽  
Xian Jun Loh
Keyword(s):  
Transfection Efficiency ◽  
Gene Transfection ◽  
Polyhedral Oligomeric Silsesquioxane ◽  
Amphiphilic Copolymers ◽  
Polyhedral Oligomeric Silsesquioxanes ◽  
Ethyl Methacrylate ◽  
Cationic Micelles ◽  
A Cell ◽  
Oligomeric Silsesquioxane

The synthesis and gene transfection efficiency of a series of amphiphilic copolymers, poly(2-(dimethylamino)ethyl methacrylate)-poly (methacrylate isobutyl polyhedral oligomeric silsesquioxane) (PDMAEMA-POSS) copolymers are reported. The hydrophobic POSS interior allows a cell-sensitizing drug such as paclitaxel to be incorporated, whereas the cationic and hydrophilic PDMAEMA corona allows the complexation of anionic DNA to form a nano-sized polyplex. These drug-encapsulated copolymers display excellent gene transfection efficiency compared with polyethylenimine or PDMAEMA homopolymers.

Functional Amphiphiles for Gene Delivery

MRS Bulletin ◽  
2005 ◽  
Vol 30 (9) ◽  
pp. 647-653 ◽  
Author(s):  
Philippe Barthélémy ◽  
Michel Camplo
Keyword(s):  
Gene Transfer ◽  
Gene Delivery ◽  
Viral Vectors ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Research Activity ◽  
Safety Issues ◽  
Significant Research

AbstractThe design of safe and efficient gene transfer vectors remains one of the key challenges in gene therapy. Despite their remarkable transfection efficiency, viral vectors suffer from known safety issues. Consequently, significant research activity has been undertaken to develop nonviral approaches to gene transfer during the last decade. Numerous academic and industrial research groups are investigating synthetic cationic vectors, such as cationic amphiphiles, with the objective of increasing the gene transfection activity. Within this area, the development of functional synthetic vectors that respond to local environmental effects have met with success. These synthetic vectors are based on mechanistic principles and represent a significant departure from earlier systems. Many of these systems for gene delivery in vitro and in vivo are discussed in this article.

scholarly journals Interaction Kinetics of Peptide Lipids-Mediated Gene Delivery

2019 ◽  
Author(s):  
Shubiao Zhang ◽  
Yinan Zhao ◽  
Yanyan Du ◽  
Yingnan Cao ◽  
Yang Xuan ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Endosomal Escape ◽  
Late Endosomes ◽  
Key Factor ◽  
Interaction Kinetics ◽  
Dna Release

Abstract Background: During the course of gene transfection, the interaction kinetics between liposomes and DNA is speculated to play very important role for blood stability, cellular uptake, DNA release and finally transfection efficiency.Results: As cationic peptide liposomes exhibited great gene transfer activities both in vitro and in vivo, two peptide lipids, containing a tri-ornithine head (LOrn3) and a mono-ornithine head (LOrn1), were chosen to further clarify the process of liposome-mediated gene delivery in this study. The results show that the electrostatically-driven binding between DNA and liposomes reached nearly 100% at equilibrium, and high affinity of LOrn3 to DNA led to fast binding rate between them. The binding process between LOrn3 and DNA conformed to the kinetics equation: y = 1.663631 × exp(-0.003427x) + 6.278163. Compared to liposome LOrn1, the liposome LOrn3/DNA lipoplex exhibited a faster and more uniform uptake in Hela cells, as LOrn3 with a tri-ornithine peptide headgroup had a stronger interaction with the negatively charged cell membrane than LOrn1. The efficient endosomal escape of DNA from LOrn3 lipoplexes was facilitated by the acidity in late endosomes, resulting in broken carbamate bonds, as well as the “proton sponge effect” of the lipid.Conclusions: The interaction kinetics is a key factor for DNA transfection efficiency. This work provided insights into peptide lipid-mediated DNA delivery that could guide the development of the next generation of delivery systems for gene therapeutics.

A bioreducible supramolecular nanoparticle gene delivery system based on cyclodextrin-conjugated polyaspartamide and adamantyl-terminated polyethylenimine

2018 ◽  
Vol 6 (5) ◽  
pp. 797-808 ◽  
Author(s):  
Yunti Zhang ◽  
Qimin Jiang ◽  
Bo Bi ◽  
Luming Xu ◽  
Jia Liu ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Delivery System ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Cellular Internalization ◽  
Gene Delivery System ◽  
Supramolecular Nanoparticles

Reduction degradable Pasp-SS-CD/Ad4-PEI/pDNA supramolecular nanoparticles via host–guest interaction exhibited improved cellular internalization and higher gene transfection efficiency with lower cytotoxicity.

The Combination of Drug or Gene Delivery System Responding to Cellular Signals (D-RECS) and Sonoporation System for Effective and Safe Gene Delivery

2009 ◽  
Vol 1237 ◽  
Author(s):  
Akira Tsuchiya ◽  
Takeshi Mori ◽  
Yuki Naritomi ◽  
Jeong-Hun Kang ◽  
Daisuke Asai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Gene Delivery ◽  
Delivery System ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Regulation System ◽  
Gene Delivery System

AbstractWe have developed new gene expression-regulating polymer that can activate transgene expression in response to target intracellular signals. Here, we tried applying sonoporation system to this gene regulation system to enhance the gene expression efficacy. Sonoporation is the method for effective gene transfection in vitro and in vivo. Therefore, the method might enhance the transfection efficiency in our polymer and realize an efficient and safe gene delivery system. Results suggested that the combination of our polymer and sonoporation could improve the gene expression compared to the system using only our polymer that transfers genes into cells via endocytosis. It also kept the ability of the gene regulation responding to cellular signals.

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