Polycations for Gene Delivery: Dilemmas and Solutions

Chen, Jie; Wang, Kui; Wu, Jiayan; Tian, Huayu; Chen, Xuesi

doi:10.1021/acs.bioconjchem.8b00688

Cited by 71 publications

(58 citation statements)

References 105 publications

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“…In addition, polycationic agents also have high nondegradability and suffer from low dissociation of the cargo from the complex in the cells due to robust interactions between the cargo and the polycation. The reported methods to reduce the toxicity of the polycationic materials include PEGylation, [ 67 ] reduction of molecular weight, [ 63c ] and controlling ring‐opening polymerization of lactones with tertiary amino‐alcohols. [ 63b,c ] Furthermore, conjugation of cholesterol, [ 68 ] cyclodextrin, [ 69 ] oligo(2‐ethyl‐2‐oxazoline), [ 70 ] fluorobenzene, [ 71 ] and alkyl chains [ 72 ] have also proven to reduce toxicity.…”

Section: Cytosolic Delivery Via Endosomal Escapementioning

confidence: 99%

Nanocarrier‐Mediated Cytosolic Delivery of Biopharmaceuticals

Xing

Wang

et al. 2020

Adv Funct Materials

125

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Biopharmaceuticals have emerged to play a vital role in disease treatment and have shown promise in the rapidly expanding pharmaceutical market due to their high specificity and potency. However, the delivery of these biologics is hindered by various physiological barriers, owing primarily to the poor cell membrane permeability, low stability, and increased size of biologic agents. Since many biological drugs are intended to function by interacting with intracellular targets, their delivery to intracellular targets is of high relevance. In this review, the authors summarize and discuss the use of nanocarriers for intracellular delivery of biopharmaceuticals via endosomal escape and, especially, the routes of direct cytosolic delivery by means including the caveolae‐mediated pathway, contact release, intermembrane transfer, membrane fusion, direct translocation, and membrane disruption. Strategies with high potential for translation are highlighted. Finally, the authors conclude with the clinical translation of promising carriers and future perspectives.

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Section: Cytosolic Delivery Via Endosomal Escapementioning

confidence: 99%

Nanocarrier‐Mediated Cytosolic Delivery of Biopharmaceuticals

Xing

Wang

et al. 2020

Adv Funct Materials

125

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“…The detailed mechanism by which EVs assists in gene transfection of PEI needs further studies. Because polycations also occur naturally (Chen et al, 2019), it can be assumed that gene transfection with EVs and natural polycations can also take place in natural systems. Although currently the expected frequency of gene transfection with natural polycations is quite low because of low concentration of natural polycations in natural systems, the use of EVs in such systems may provide a promising all-natural transfection system.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Nanovesicle Enhanced Gene Transfection Using Polyethyleneimine in HEK293T Cells and Zebrafish Embryos

Zhang

Wen

Zhang

et al. 2020

Front. Bioeng. Biotechnol.

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It is a hot topic to improve efficiency and decrease toxicity of gene transfection reagents. The extracellular nanovesicles (EVs) that are released by cells play an important role in intercellular communication and are naturally designed for genetic exchange between cells. Here, we show that the EVs have a large beneficial effect in polyethyleneimine (PEI)-mediated transfection of a GFP-encoding plasmid into HEK293T cells. An improvement of transfection efficiency of ∼500% and a decrease in toxicity were observed in a specific concentration range of PEI. The EVs also greatly improved the transfection of the same plasmid into zebrafish embryos. To verify the generality of this gene transfection approach, we also tested the cell viability and gene transfection efficiency using two other plasmids (EpTEN and ELuc) and in another cell line (A549). The measured increase in transfection efficiency makes EV a promising candidate for enhancement of the quality of current PEI-based transfection technique.

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“…To achieve better delivery performance, synthetic gene carriers must overcome many challenges, such as low gene loading/release efficiency, cytotoxicity, inefficient endosome escape and poor nucleus entry. 53,54 For cationic micelles, physical stability is fundamental to withstanding dissociation and the premature release of their cargo after entering into the bloodstream. A significant barrier to the transfection efficiency of cationic micelles is their stability.…”

Section: The Key Factors Of Micelles As Gene Carriersmentioning

confidence: 99%

Cationic micelle: A promising nanocarrier for gene delivery with high transfection efficiency

Wang

Ding

Zhang

et al. 2019

The Journal of Gene Medicine

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Micelles have demonstrated an excellent ability to deliver several different types of therapeutic agents, including chemotherapy drugs, proteins, small‐interfering RNA and DNA, into tumor cells. Cationic micelles, comprising self‐assemblies of amphiphilic cationic polymers, have exhibited tremendous promise with respect to the delivery of therapy genes and gene transfection. To date, research in the field has focused on achieving an enhanced stability of the micellar assembly, prolonged circulation times and controlled release of the gene. This review focuses on the micelles as a nanosized carrier system for gene delivery, the system‐related modifications for cytoplasm release, stability and biocompatibility, and clinic trials. In accordance with the development of synthetic chemistry and self‐assembly technology, the structures and functionalities of micelles can be precisely controlled, and hence the synthetic micelles not only efficiently condense DNA, but also facilitate DNA endocytosis, endosomal escape, DNA uptake and nuclear transport, resulting in a comparable gene transfection of virus.

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Polycations for Gene Delivery: Dilemmas and Solutions

Cited by 71 publications

References 105 publications

Nanocarrier‐Mediated Cytosolic Delivery of Biopharmaceuticals

Nanocarrier‐Mediated Cytosolic Delivery of Biopharmaceuticals

Extracellular Nanovesicle Enhanced Gene Transfection Using Polyethyleneimine in HEK293T Cells and Zebrafish Embryos

Cationic micelle: A promising nanocarrier for gene delivery with high transfection efficiency

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