Low generation PAMAM-based nanomicelles as ROS-responsive gene vectors with enhanced transfection efficacy and reduced cytotoxicity in vitro

Xu, Chen-Tao; Chen, Guang; Nie, Xuan; Wang, Long‐Hai; Ding, Shenggang; You, Ye‐Zi

doi:10.1039/c6nj04129a

Cited by 16 publications

(21 citation statements)

References 36 publications

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“…This is probably the case of hollow spheres of PPS and collagen, which show oxidant‐induced nanoporation and potentially also enzymatic degradation upon oxidation . In the second case (avidity), oxidation can remove the necessary proximity between positive charges (either disrupting hydrophobic association, or cleaving the polymer chain), thereby reversing the complexation of polycations with nucleic acids.…”

Section: Oxidation (Ros)‐responsive Materialsmentioning

confidence: 99%

Oxidation‐Responsive Materials: Biological Rationale, State of the Art, Multiple Responsiveness, and Open Issues

El-Mohtadi

d’Arcy

Tirelli

2018

Macromol. Rapid Commun.

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In this review, a general introduction to biological oxidants (focusing on reactive oxygen species, ROS) and the biomedical rationale behind the development of materials capable of responding to ROS is provided. The state of the art for preparative aspects and mechanistic responses of the most commonly used macromolecular ROS‐responsive systems, including polysulfides, polyselenides, polythioketals, polyoxalates, and also oligoproline‐ and catechol‐based materials, is subsequently given. The endowment of multiple responsiveness, with specific emphasis on the cases where a molecular logic gate behavior can be obtained, is focused on. Finally, fundamental open issues, which include implications of the “drug”‐like character of ROS‐responsive materials (inherent anti‐inflammatory behavior) and the poor quantitative understanding of ROS roles in biology, are discussed.

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Section: Oxidation (Ros)‐responsive Materialsmentioning

confidence: 99%

Oxidation‐Responsive Materials: Biological Rationale, State of the Art, Multiple Responsiveness, and Open Issues

El-Mohtadi

d’Arcy

Tirelli

2018

Macromol. Rapid Commun.

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“…Polymer/DNA (1 μg) complexes were added to each well and incubated at 37 °C. Control reagents 25 KDa PEI (at a w / w ratio of 1.4, N/P = 10) [ 4 , 14 , 17 ] and Lipofectamine 2000 were formulated with DNA based upon their recommended protocols. After 4 h of incubation, the transfection medium was replaced with fresh complete medium containing 10% FBS and further incubated for 20 h. The images of GFP expressed cells were taken with an inverted fluorescence microscope (Nikon Eclipse TE 2000E, Nikon, Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

“…Due to the high transfection efficiency (TE), viral carriers are a commonly used method of gene delivery. However, their immunogenicity, toxicity, limited DNA packaging capacity, and difficulty in large-scale production have impeded their development and clinic applications [ 4 , 5 ]. In attempt to overcome these barriers, a broad range of versatile and efficient non-viral gene vectors have been developed.…”

Section: Introductionmentioning

confidence: 99%

Aromatic Thioacetal-Bridged ROS-Responsive Nanoparticles as Novel Gene Delivery Vehicles

Guo

Liu

et al. 2018

Molecules

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In this report, a series of polycations are designed and synthesized by conjugating reactive oxygen species (ROS)-responsive thioacetal-linkers to low molecular weight (LMW) polyethylenimine (PEI) via ring-opening polymerization. Their structure–activity relationships (SARs) as gene delivery vectors are systematically studied. Although the MWs of the target polymers are only ~9 KDa, they show good DNA binding ability. The formed polyplexes, which are stable toward serum but decomposed under ROS-conditions, have appropriate sizes (180~300 nm) and positive zeta-potentials (+35~50 mV). In vitro experiments reveal that these materials have low cytotoxicity, and higher transfection efficiency (TE) than controls. Furthermore, the title polymers exhibit excellent serum tolerance. With the present of 10% serum, the TE of the polymers even increases up to 10 times higher than 25 KDa PEI and 9 times higher than Lipofectamine 2000. The SAR studies also reveal that electron-withdrawing groups on the aromatic ring in 4a may benefit to balance between the DNA condensation and release for efficient gene transfection.

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“…Typically, normal blood remains well buffered and constant around pH 7.4, whereas acidification occurs in a tumor microenvironment (pH 6.8) . After internalization into cancer cells, drug loaded nanocarriers will confront the pH changes from early endosomes (pH 5.5–6.0) to later lysosomes (pH 5.0–5.5) .…”

Section: Stimulus‐responsive Micelles For Effective Gene Deliverymentioning

confidence: 99%

“…Typically, normal blood remains well buffered and constant around pH 7.4, whereas acidification occurs in a tumor microenvironment (pH 6.8). 96 After internalization into cancer cells, drug loaded nanocarriers will confront the pH changes from early endosomes (pH 5.5-6.0) 97 to later lysosomes (pH 5.0-5.5). 98 The construction of pH-sensitive "detachable" polyethylene glycol (PEG) shells is an effective approach for facilitating gene release.…”

Section: Ph-responsive Micellesmentioning

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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Low generation PAMAM-based nanomicelles as ROS-responsive gene vectors with enhanced transfection efficacy and reduced cytotoxicity in vitro

Abstract: ROS-responsive cationic nanomicelles formed from amphiphilic PPS–SS–PAMAMG2.0 conjugates exhibit high transfection efficacy and low cytotoxicity.

Cited by 16 publications

References 36 publications

Oxidation‐Responsive Materials: Biological Rationale, State of the Art, Multiple Responsiveness, and Open Issues

Oxidation‐Responsive Materials: Biological Rationale, State of the Art, Multiple Responsiveness, and Open Issues

Aromatic Thioacetal-Bridged ROS-Responsive Nanoparticles as Novel Gene Delivery Vehicles

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

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