Low molecular weight PEI-based fluorinated polymers for efficient gene delivery

Xiao, Yaping; Zhang, Ji; Liu, Yanhong; Zhang, Ju-Hui; Yu, Qing-Ying; Huang, Zheng; Yu, Xiao‐Qi

doi:10.1016/j.ejmech.2018.11.041

Cited by 26 publications

(10 citation statements)

References 43 publications

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“…The best way to compare the overall effectiveness in vitro of new gene delivery vectors between laboratories is to gauge their performances with respect to those of suitable benchmarks of seemingly well-known behavior. PEIs, together with commercially available reagents and kits such as those belonging to the Lipofectamine series and jetPEI ® , have largely been used in a number of studies in this regard [57,60,69,[175][176][177][178]. The way any benchmark transfectant behaves and performs is, however, critically dependent on a variety of parameters and in-home experimental conditions.…”

Section: Discussionmentioning

confidence: 99%

Non-Viral in Vitro Gene Delivery: It is Now Time to Set the Bar!

et al. 2020

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Transfection by means of non-viral gene delivery vectors is the cornerstone of modern gene delivery. Despite the resources poured into the development of ever more effective transfectants, improvement is still slow and limited. Of note, the performance of any gene delivery vector in vitro is strictly dependent on several experimental conditions specific to each laboratory. The lack of standard tests has thus largely contributed to the flood of inconsistent data underpinning the reproducibility crisis. A way researchers seek to address this issue is by gauging the effectiveness of newly synthesized gene delivery vectors with respect to benchmarks of seemingly well-known behavior. However, the performance of such reference molecules is also affected by the testing conditions. This survey points to non-standardized transfection settings and limited information on variables deemed relevant in this context as the major cause of such misalignments. This review provides a catalog of conditions optimized for the gold standard and internal reference, 25 kDa polyethyleneimine, that can be profitably replicated across studies for the sake of comparison. Overall, we wish to pave the way for the implementation of standardized protocols in order to make the evaluation of the effectiveness of transfectants as unbiased as possible.

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Section: Discussionmentioning

confidence: 99%

Non-Viral in Vitro Gene Delivery: It is Now Time to Set the Bar!

et al. 2020

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“…For potential application such as cancer, ROS-sensitive linker can be exploited owing to the high ROS level in tumors, among which thioether are typical with direct cleavage ability [ 39 ]. On the other hand, fluorinated chains grafting has been proven effective to endow the polycations with good serum stability owing to the hydrophobicity and lipophobicity, and enhance cellular uptake and endosomal escape due to the affinity to the membrane [ 24 ]. Hence, we propose a combination of crosslinking strategies and fluorination techniques to construct gene carriers with excellent transfection efficiency and reduced cytotoxicity.…”

Section: Discussionmentioning

confidence: 99%

ROS responsive polyethylenimine-based fluorinated polymers for enhanced transfection efficiency and lower cytotoxicity

Hua

Yang

Chen

et al. 2022

Bosn J of Basic Med Sci

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Cationic polymer polyethylenimine (PEI) plays a crucial role in gene delivery. However, high molecular weight PEI leads to higher efficient transfection efficacy and higher cytotoxicity while low molecular weight PEI exhibits lower transfection performance with lower toxicity. Therefore, effective chemical modification of PEI is required to enhance transfection activity and improve biocompatibility. Here, reactive oxygen species (ROS) responsive PEI-based fluorinated polymers (TKPF) with three degrees of fluorination (TKPF12.5%, TKPF25% and TKPF50%) were designed and synthesized by crosslinking low molecular weight PEI (PEI 1.8K) with a thioketal (TK) linker and then modifying heptafluorobutyric anhydride onto their surface. Such gene vectors exhibited the following features: (1) fluorination reduced the positive charge density and endowed hydrophobic and lipophobic characteristics to resist serum interactions; (2) The fluorophilic effect mediated efficient cellular uptake and endosomal escape; (3) ROS-responsive TK linker allowed the polyplex disassembly to decrease the cytotoxicity of the polycations and improve the release of payloads at specific sites. TKPFs attained superior transfection efficiency in multiple cell lines (293TN cells and B16F10 cells) in vitro and showed excellent biocompatibility. Notably, TKPFs also exhibited great serum resistance in gene delivery and TKPF50% transfected nearly 80% cells in the presence of 70% FBS. These results demonstrates that the fluorination and ROS responsiveness combined polycations are excellent gene-delivery vectors with serum-resistant capacity for further application.

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“…And because its highly delivery efficiency and protection effects for DNA, flexible properties, facile synthesis, robustness, cationic polymers have become the intense research as non-viral gene delivery systems. [35][36][37] Besides, the MNP also be widely used for gene delivery for its superparamagnetism, low toxicity, biocompatibility, nonimmunogenicity, and high effective surface. 38 Besides, our nanoparticles' diameter is appropriate.…”

Section: The Physicochemical Property Of Mnpmentioning

confidence: 99%

The targeted inhibition of prostate cancer by iron-based nanoparticles based on bioinformatics

et al. 2020

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Prostate cancer is an epithelial malignant tumor of the prostate, and it is one of the malignant tumors with a high incidence of urogenital system in men. The local treatment of prostate cancer is mainly radical resection and radical radiotherapy, but they are not applicable to advanced prostate cancer. Systemic therapy mainly includes targeted therapy and immunotherapy which could cause many complications, and will affect the prognosis and quality of life of patients. It is urgent to find new treatments for prostate cancer. Bioinformatics offers hope for us to find reliable therapeutic targets. Bioinformatics can use the tumor informations in database and analyze them to screen out the best differentially expressed genes. Using the selected differentially expressed genes as targets, a gene interference plasmid was designed, and the constructed plasmid was used for targeted gene therapy. There are some problems about gene therapy that need to be solved, such as how to transfer genes to target cells is also an important challenge. Due to their large molecular weight and hydrophilic nature, they cannot enter cells through passive diffusion mechanisms. Here we synthesized a DNA carrier used surface modified iron based nanoparticles, and used it to load plasmid including ShRNA which can inhibit the expression of oncogene SLC4A4 selected by bioinformatics’ method. After that we use this iron based nanoparticles/plasmid DNA nanocomposite to treat prostate cancer cells in vitro and in vivo. The target gene SLC4A4 we had selected using bioinformatics had a strong effect on the proliferation of prostate cells; Our nanocomposite could inhibit the expression of SLC4A4 effectively, it had strong inhibitory effects on prostate cancer cells both in vivo and in vitro, and can be used as a potential method for prostate cancer treatment.

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Low molecular weight PEI-based fluorinated polymers for efficient gene delivery

Cited by 26 publications

References 43 publications

Non-Viral in Vitro Gene Delivery: It is Now Time to Set the Bar!

Non-Viral in Vitro Gene Delivery: It is Now Time to Set the Bar!

ROS responsive polyethylenimine-based fluorinated polymers for enhanced transfection efficiency and lower cytotoxicity

The targeted inhibition of prostate cancer by iron-based nanoparticles based on bioinformatics

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