Synthesis of bifunctional molecules containing [12]aneN3 and coumarin moieties as effective DNA condensation agents and new non-viral gene vectors

Bifunctional molecules with different combinations of [12]aneN3 and coumarin moieties were successfully applied in DNA condensation and gene transfection.

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Synthesis and gene transfection activity of cyclen-based cationic lipids with asymmetric acyl-cholesteryl hydrophobic tails

Organic & Biomolecular Chemistry ◽

10.1039/c4ob00384e ◽

2014 ◽

Vol 12 (21) ◽

pp. 3484-3492 ◽

Cited By ~ 10

Author(s):

Bao-Quan Liu ◽

Wen-Jing Yi ◽

Ji Zhang ◽

Qiang Liu ◽

Yan-Hong Liu ◽

...

Keyword(s):

Gene Transfection ◽

Cationic Lipids ◽

Viral Gene ◽

Gene Vectors

Novel cyclen-based cationic lipids with asymmetric acyl-cholesteryl hydrophobic tails were synthesized and applied as non-viral gene vectors.

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Transient stealth coating of liver sinusoidal wall by anchoring two-armed PEG for retargeting nanomedicines

Science Advances ◽

10.1126/sciadv.abb8133 ◽

2020 ◽

Vol 6 (26) ◽

pp. eabb8133 ◽

Cited By ~ 4

Author(s):

Anjaneyulu Dirisala ◽

Satoshi Uchida ◽

Kazuko Toh ◽

Junjie Li ◽

Shigehito Osawa ◽

...

Keyword(s):

Transfection Efficiency ◽

Gene Transfection ◽

Critical Issue ◽

Viral Gene ◽

Liver Sinusoids ◽

Gene Vectors ◽

Sinusoidal Endothelium ◽

Poly Ethylene ◽

Peg Coating

A major critical issue in systemically administered nanomedicines is nonspecific clearance by the liver sinusoidal endothelium, causing a substantial decrease in the delivery efficiency of nanomedicines into the target tissues. Here, we addressed this issue by in situ stealth coating of liver sinusoids using linear or two-armed poly(ethylene glycol) (PEG)–conjugated oligo(l-lysine) (OligoLys). PEG-OligoLys selectively attached to liver sinusoids for PEG coating, leaving the endothelium of other tissues uncoated and, thus, accessible to the nanomedicines. Furthermore, OligoLys having a two-armed PEG configuration was ultimately cleared from sinusoidal walls to the bile, while OligoLys with linear PEG persisted in the sinusoidal walls, possibly causing prolonged disturbance of liver physiological functions. Such transient and selective stealth coating of liver sinusoids by two-arm-PEG-OligoLys was effective in preventing the sinusoidal clearance of nonviral and viral gene vectors, representatives of synthetic and nature-derived nanomedicines, respectively, thereby boosting their gene transfection efficiency in the target tissues.

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Zn-promoted gene transfection efficiency for non-viral vectors: a mechanism study

New Journal of Chemistry ◽

10.1039/d1nj02115j ◽

2021 ◽

Author(s):

Xiao-Qi Yu ◽

Rui-Mo Zhao ◽

Yu Guo ◽

Hui-Zhen Yang ◽

Ji Zhang

Keyword(s):

Gene Therapy ◽

Nucleic Acid ◽

Gene Delivery ◽

Viral Vectors ◽

Transfection Efficiency ◽

Gene Transfection ◽

Viral Gene ◽

Mechanism Study ◽

High Affinity ◽

Gene Vectors

The development of cationic non-viral gene vectors that may overcome the obstacles in gene delivery is of great significance to gene therapy. Metallic complexes with high affinity to nucleic acid...

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Polycations with excellent gene transfection ability based on PVP-g-PDMAEMA with random coil and micelle structures as non-viral gene vectors

Journal of Materials Chemistry B ◽

10.1039/c4tb01754d ◽

2015 ◽

Vol 3 (5) ◽

pp. 911-918 ◽

Cited By ~ 17

Author(s):

Yuhua Song ◽

Tingbin Zhang ◽

Xiaoyan Song ◽

Ling Zhang ◽

Chunqiu Zhang ◽

...

Keyword(s):

Transfection Efficiency ◽

Gene Transfection ◽

Random Coil ◽

Viral Gene ◽

Core Shell ◽

Random Coils ◽

Gene Vectors ◽

Spherical Core ◽

Self Assembled

PVP-g-PDMAEMA formed random coils in water and PVP-g-PDMAEMA-b-PMMA self-assembled into spherical core–shell micelles. Both displayed excellent pDNA compacting abilities at an extremely low N/P ratio, with PVP-g-PDMAEMA-b-PMMA also showing excellent gear transfection efficiency.

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Effective and reversible DNA condensation induced by bifunctional molecules containing macrocyclic polyamines and naphthyl moieties

Bioorganic & Medicinal Chemistry ◽

10.1016/j.bmc.2011.11.069 ◽

2012 ◽

Vol 20 (2) ◽

pp. 801-808 ◽

Cited By ~ 21

Author(s):

Hao Yan ◽

Zhi-Fen Li ◽

Zhi-Fo Guo ◽

Zhong-Lin Lu ◽

Feng Wang ◽

...

Keyword(s):

Dna Condensation ◽

Bifunctional Molecules ◽

Macrocyclic Polyamines

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Structure–activity relationship studies of symmetrical cationic bolasomes as non-viral gene vectors

Journal of Materials Chemistry B ◽

10.1039/c6tb00870d ◽

2016 ◽

Vol 4 (33) ◽

pp. 5575-5584 ◽

Cited By ~ 10

Author(s):

Zheng Huang ◽

Yi-Mei Zhang ◽

Qian Cheng ◽

Ji Zhang ◽

Yan-Hong Liu ◽

...

Keyword(s):

Gene Delivery ◽

Structure Activity Relationship ◽

Activity Relationship ◽

Viral Gene ◽

Structure Activity ◽

Gene Delivery Vectors ◽

Gene Vectors

Bolalipids based on lysine or cyclen headgroups were synthesized and their structure–activity relationship as gene delivery vectors was studied.

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A pH and Redox Dual Responsive 4-Arm Poly(ethylene glycol)-block-poly(disulfide histamine) Copolymer for Non-Viral Gene Transfection in Vitro and in Vivo

International Journal of Molecular Sciences ◽

10.3390/ijms15059067 ◽

2014 ◽

Vol 15 (5) ◽

pp. 9067-9081 ◽

Cited By ~ 13

Author(s):

Kangkang An ◽

Peng Zhao ◽

Chao Lin ◽

Hongwei Liu

Keyword(s):

Ethylene Glycol ◽

Gene Transfection ◽

Viral Gene ◽

Poly Ethylene Glycol ◽

Dual Responsive ◽

Poly Ethylene

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Aliphatic Quaternary Ammonium Functionalized Nanogels for Gene Delivery

Pharmaceutics ◽

10.3390/pharmaceutics13111964 ◽

2021 ◽

Vol 13 (11) ◽

pp. 1964

Author(s):

Huaiying Zhang ◽

Damla Keskin ◽

Willy H. de Haan-Visser ◽

Guangyue Zu ◽

Patrick van Rijn ◽

...

Keyword(s):

Gene Delivery ◽

Tertiary Amine ◽

Quaternary Ammonium ◽

Gene Transfection ◽

Genetic Material ◽

Cationic Lipid ◽

Endosomal Escape ◽

Hereditary Diseases ◽

Viral Gene

Gene therapy is a promising treatment for hereditary diseases, as well as acquired genetic diseases, including cancer. Facing the complicated physiological and pathological environment in vivo, developing efficient non-viral gene vectors is needed for their clinical application. Here, poly(N-isopropylacrylamide) (p(NIPAM)) nanogels are presented with either protonatable tertiary amine groups or permanently charged quaternized ammonium groups to achieve DNA complexation ability. In addition, a quaternary ammonium-functionalized nanogel was further provided with an aliphatic moiety using 1-bromododecane to add a membrane-interacting structure to ultimately facilitate intracellular release of the genetic material. The ability of the tertiary amine-, quaternized ammonium-, and aliphatic quaternized ammonium-functionalized p(NIPAM) nanogels (i.e., NGs, NGs-MI, and NGs-BDD, respectively) to mediate gene transfection was evaluated by fluorescence microscopy and flow cytometry. It is observed that NGs-BDD/pDNA complexes exhibit efficient gene loading, gene protection ability, and intracellular uptake similar to that of NGs-MI/pDNA complexes. However, only the NGs-BDD/pDNA complexes show a notable gene transfer efficiency, which can be ascribed to their ability to mediate DNA escape from endosomes. We conclude that NGs-BDD displays a cationic lipid-like behavior that facilitates endosomal escape by perturbing the endosomal/lysosomal membrane. These findings demonstrate that the presence of aliphatic chains within the nanogel is instrumental in accomplishing gene delivery, which provides a rationale for the further development of nanogel-based gene delivery systems.

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