Hydrophobic chain modified low molecular weight polyethylenimine for efficient antigen delivery

Wang, Hui; Chen, Jian; Ying, Jiajun; Xu, Yuhong; Sheng, Ruilong

doi:10.1039/c5ra25919c

Cited by 9 publications

(8 citation statements)

References 40 publications

(40 reference statements)

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“…Among the three boronic‐ester‐containing polysulfoniums, 6CBE has the highest hydrophobicity (hydrophobicity: EOBE < 4CBE < 6CBE). Hydrophobilization of cationic polymers such as low‐molecular‐weight PEI and polylysine was found to increase the gene transfection efficiency.…”

Section: Resultsmentioning

confidence: 99%

Intracellularly Disintegratable Polysulfoniums for Efficient Gene Delivery

Zhu

Huang

Liu

et al. 2017

Adv Funct Materials

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Amine-based cationic polymers have been extensively explored as nonviral carriers for gene delivery, but inefficient intracellular unpacking of polymer/ DNA complexes (polyplexes) to release plasmids is still a key limiting step to high transfection efficiency. Furthermore, the amine-resulting cationic charges in the polymer chains, and even their degraded fragments, inherently interfere with transgene expression. A cationic polymer capable of converting to uncharged fragments once inside cells would not only quickly release the DNA, but also not interfere with the gene transcription process for efficient gene expression and low toxicity. A new class of polysulfoniums that can degrade into neutral thioether fragments triggered by reactive oxygen species (ROS) is reported. The polysulfoniums condense DNA into nanosized polyplexes, which can be quickly internalized and efficiently escape from endo/lysosomes. In cancer cells, the oxidation of the boronic acid/ester by the elevated ROS levels triggers polysulfonium to break down into neutral thioether fragments, efficiently releasing DNA for gene expression. More importantly, the polyplexes have excellent serum resistance; in vivo, they efficiently deliver the suicide gene pTRAIL to intraperitoneal tumors eliciting effective anticancer activity.

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Section: Resultsmentioning

confidence: 99%

Intracellularly Disintegratable Polysulfoniums for Efficient Gene Delivery

Zhu

Huang

Liu

et al. 2017

Adv Funct Materials

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“…13,[17][18][19][20][21][22][23][24][25] Since high molecular weight PEI induces more toxicity, there are several reports suggesting the application of low molecular weight PEI (LMW PEI) as the core of the transfection vector and modifying it to increase its transfection efficiency. 15,[26][27][28][29][30][31][32] Considering the effect of hydrophobic modification of PEI in increasing the transfection efficiency, we hypothesized that cross-linking LMW PEIs using potentially biodegradable linkages such as amides enhances its gene transfer ability with minimal toxic effects. CD200 is a membrane glycoprotein which has been shown to cause immune suppression via its receptor CD200R.…”

Section: Introductionmentioning

confidence: 99%

Preparation, characterization, and transfection efficiency of low molecular weight polyethylenimine-based nanoparticles for delivery of the plasmid encoding CD200 gene

Nouri¹,

Sadeghpour²,

Heidari³

et al. 2017

IJN

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Various strategies have been utilized to improve both gene transfer efficiency and cell-induced toxicity of polyethylenimine (PEI), the most extensively investigated cationic polymeric vector. In this study, we sought to enhance transfection efficiency of low molecular weight PEI (LMW PEI) while maintaining its low toxicity by cross-linking LMW PEI via succinic acid linker. These modifications were designed to improve the hydrophilic–hydrophobic balance of the polymer, by enhancing the buffering capacity and maintaining low cytotoxic effects of the final conjugate. Decreased expression of CD200 in the central nervous system has been considered as one of the proposed mechanisms associated with neuroinflammation in multiple sclerosis; therefore, we selected plasmid-encoding CD200 gene for transfection using the modified PEI derivatives. Dynamic light scattering experiments demonstrated that the modified PEIs were able to condense plasmid DNA and form polyplexes with a size of approximately 130 nm. The highest level of CD200 expression was achieved at a carrier to plasmid ratio of 8, where the expression level was increased by 1.5 fold in the SH-SY5Y cell line, an in vitro model of neurodegenerative disorders. Furthermore, the results of in vivo imaging of the LMW PEI-based nanoparticles in the mouse model of multiple sclerosis revealed that fluorescently labeled plasmid encoding CD200 was distributed from the injection site to various tissues and organs including lymph nodes, liver, brain, and finally, kidneys. The nanoparticles also showed the ability to cross the blood–brain barrier and enter the periventricular area.

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“…Polyethylenimine-based micro/nanoparticles as adjuvants between the properties of the synthesized hydrophobicmodified PEI and the vaccine potency still needs further investigation. 50 CPPs are another valuable species that can optimize the interactions between cell membranes and the PEI-based polyplex. CPPs, characterized by the polycationic amino acid residues (ie, arginine and lysine), have been known for their specialized ability to penetrate the cellular membranes.…”

mentioning

confidence: 99%

Polyethylenimine-based micro/nanoparticles as vaccine adjuvants

Shen¹,

Li²,

Zhang³

et al. 2017

IJN

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Vaccines have shown great success in treating and preventing tumors and infections, while adjuvants are always demanded to ensure potent immune responses. Polyethylenimine (PEI), as one of the well-studied cationic polymers, has been used as a transfection reagent for decades. However, increasing evidence has shown that PEI-based particles are also capable of acting as adjuvants. In this paper, we briefly review the physicochemical properties and the broad applications of PEI in different fields, and elaborate on the intracellular processes of PEI-based vaccines. In addition, we sum up the proof of their in vivo and clinical applications. We also highlight some mechanisms proposed for the intrinsic immunoactivation function of PEI, followed by the challenges and future perspectives of the applications of PEI in the vaccines, as well as some strategies to elicit the desirable immune responses.

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Hydrophobic chain modified low molecular weight polyethylenimine for efficient antigen delivery

Abstract: Developing new therapeutic vaccines to promote antigen cross-presentation in antigen-presenting cells, especially dendritic cells, is regarded as a promising approach to prime antigen-specific T cell responses against tumor cells.

Cited by 9 publications

References 40 publications

Intracellularly Disintegratable Polysulfoniums for Efficient Gene Delivery

Intracellularly Disintegratable Polysulfoniums for Efficient Gene Delivery

Preparation, characterization, and transfection efficiency of low molecular weight polyethylenimine-based nanoparticles for delivery of the plasmid encoding CD200 gene

Polyethylenimine-based micro/nanoparticles as vaccine adjuvants

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