Cytotoxic Impacts of Linear and Branched Polyethylenimine Nanostructures in A431 Cells

Kafil, Vala; Omidi, Yadollah

doi:10.5681/bi.2011.004

Cited by 96 publications

(37 citation statements)

References 22 publications

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“…The cell viabilities in cells treated with PEI-SA and PEI-BSA were greater than 70% at a concentration of 10 μg/mL, while the cell viability in cells treated with PEI was just 55%. Branched PEI (25 kDa) has been previously reported to have high cell toxicity . PEI toxicity appears to be mainly associated with the high net positive charge on the polymer due to the numerous amino groups present in the polymeric backbone (Figure ).…”

Section: Results and Discussionsupporting

confidence: 91%

Freezing-Assisted Gene Delivery Combined with Polyampholyte Nanocarriers

Ahmed

Nakaji-Hirabayashi

Watanabe

et al. 2017

ACS Biomater. Sci. Eng.

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Physical methodologies such as electroporation and the gene-gun technology have been widely used for transfection; however, their applicability is limited because they lead to cell damage and low cell viability. Therefore, to address these limitations we developed a new freeze concentration-based gene transfection system that provides enhanced in vitro gene delivery compared to that provided by the commercially available systems. The system employs a facile freeze concentration step, whereby cells are simply frozen to very low temperatures in the presence of polymer-pDNA complexes. As part of system development, we also synthesized a low toxicity polyethylenimine (PEI)-based polyampholyte prepared through succinylation with butylsuccinic anhydride. In aqueous solution, this modified polyampholyte self-assembles to form small (20 nm diameter), positively charged (net surface charge of 35 mV), nanoparticles through a combination of hydrophobic and electrostatic interactions. Agarose gel electrophoresis analysis indicated that the polyampholyte nanoparticle was able to form a complex with pDNA that provided stability against nuclease degradation. Using transfection of HEK-293T cells, we demonstrated that a combination of polyampholyte: pDNA, at an appropriate ratio, and the freeze concentration method resulted in significant enhancement of GFP and luciferase expression compared to commercially available carriers. Endosomal escape of pDNA was also found to be increased when using the modified polyampholyte compared to branched PEI. This study suggests that the efficient combination of freeze concentration and the modified polyampholyte described here has great potential for in vitro gene therapy.

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Section: Results and Discussionsupporting

confidence: 91%

Freezing-Assisted Gene Delivery Combined with Polyampholyte Nanocarriers

Ahmed

Nakaji-Hirabayashi

Watanabe

et al. 2017

ACS Biomater. Sci. Eng.

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“…Biodegradability is important to avoid bioaccumulation. Low charge is important because polyplexes with excess positive charge can interact with cellular components and inhibit normal cellular processes, which leads to substantial toxicity. − Hydrophobicity is another desired feature to help stabilize the polyplexes, especially for polymers with low cationic density . Acid sensitivity is important for endosomal escape and unpackaging of genes.…”

Section: Discussionmentioning

confidence: 99%

Multifunctional Poly(amine-co-ester-co-orthoester) for Efficient and Safe Gene Delivery

Zhang

Cui

Deng

et al. 2016

ACS Biomater. Sci. Eng.

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Cationic polymers are used for non-viral gene delivery, but current materials lack the functionality to address the multiple barriers involved in gene delivery. Here we describe the rational design and synthesis of a new family of quaterpolymers with unprecedented multifunctionality: acid sensitivity, low cationic charge, high hydrophobicity, and biodegradability, all of which are essential for efficient and safe gene delivery. The polymers were synthesized via lipase-catalyzed polymerization of ortho ester diester, lactone, dialkyl diester, and amino diol monomers. Polymers containing ortho ester groups exhibited acid-sensitive degradation at endosomal pH (4~5), facilitated efficient endosomal escape and unpackaging of the genes, and were efficient in delivering genetic materials to HEK293 cells, human glioma cells, primary mouse melanoma cells, and human umbilical vein endothelial cells (HUVECs). We also developed a highly efficient lyophilized formulation of the nanoparticles, which could be stored for a month without loss of efficiency.

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“…Xun Sun’s group demonstrated that cationic cyclodextrin-polyethylenimine 2k conjugates (CP 2k) which are complexed with anionic mRNA-encoding HIV gp120 induce strong systemic and mucosal anti-HIV immune responses [ 176 ]. Nevertheless, toxicity problems have been reported with polyethyleneimine and lipid nanoparticles when these are injected via the nasal route [ 177 , 178 , 179 ]. Improving the benefit-risk balance and the efficacy of these mucosal RNA vaccines is the subject of numerous ongoing studies.…”

Section: Stxb Functions As a Mucosal Delivery Vectormentioning

confidence: 99%

STxB as an Antigen Delivery Tool for Mucosal Vaccination

Tartour

Johannes

2022

Toxins

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Immunotherapy against cancer and infectious disease holds the promise of high efficacy with minor side effects. Mucosal vaccines to protect against tumors or infections disease agents that affect the upper airways or the lung are still lacking, however. One mucosal vaccine candidate is the B-subunit of Shiga toxin, STxB. In this review, we compare STxB to other immunotherapy vectors. STxB is a non-toxic protein that binds to a glycosylated lipid, termed globotriaosylceramide (Gb3), which is preferentially expressed by dendritic cells. We review the use of STxB for the cross-presentation of tumor or viral antigens in a MHC class I-restricted manner to induce humoral immunity against these antigens in addition to polyfunctional and persistent CD4+ and CD8+ T lymphocytes capable of protecting against viral infection or tumor growth. Other literature will be summarized that documents a powerful induction of mucosal IgA and resident memory CD8+ T cells against mucosal tumors specifically when STxB-antigen conjugates are administered via the nasal route. It will also be pointed out how STxB-based vaccines have been shown in preclinical cancer models to synergize with other therapeutic modalities (immune checkpoint inhibitors, anti-angiogenic therapy, radiotherapy). Finally, we will discuss how molecular aspects such as low immunogenicity, cross-species conservation of Gb3 expression, and lack of toxicity contribute to the competitive positioning of STxB among the different DC targeting approaches. STxB thereby appears as an original and innovative tool for the development of mucosal vaccines in infectious diseases and cancer.

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Cytotoxic Impacts of Linear and Branched Polyethylenimine Nanostructures in A431 Cells

Cited by 96 publications

References 22 publications

Freezing-Assisted Gene Delivery Combined with Polyampholyte Nanocarriers

Freezing-Assisted Gene Delivery Combined with Polyampholyte Nanocarriers

Multifunctional Poly(amine-co-ester-co-orthoester) for Efficient and Safe Gene Delivery

STxB as an Antigen Delivery Tool for Mucosal Vaccination

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