Engineered PEI-piperazinyl nanoparticles as efficient gene delivery vectors: evidence from both in vitro and in vivo studies

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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Nuclear location signal peptide–modified poly (ethyleneimine)/DNA complexes: An efficient gene delivery vector in vitro and in vivo

Journal of Bioactive and Compatible Polymers ◽

10.1177/0883911513483507 ◽

2013 ◽

Vol 28 (3) ◽

pp. 218-232 ◽

Cited By ~ 8

Author(s):

Hua Zhang ◽

Zhongyan Liang ◽

Wanli Li ◽

Fangcai Li ◽

Qixin Chen

Keyword(s):

Gene Delivery ◽

Signal Peptide ◽

Dna Complexes ◽

Gene Delivery Vector ◽

Delivery Vector ◽

Nuclear Location Signal ◽

Efficient Gene ◽

Nuclear Location

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Tumor-Targeted Gene Delivery Using Poly(Ethylene Glycol)-Modified Gelatin Nanoparticles: In Vitro and in Vivo Studies

Pharmaceutical Research ◽

10.1007/s11095-005-4590-3 ◽

2005 ◽

Vol 22 (6) ◽

pp. 951-961 ◽

Cited By ~ 141

Author(s):

Goldie Kaul ◽

Mansoor Amiji

Keyword(s):

Gene Delivery ◽

Ethylene Glycol ◽

In Vivo Studies ◽

Poly Ethylene Glycol ◽

Gelatin Nanoparticles ◽

Targeted Gene Delivery ◽

Poly Ethylene

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Poly(ethylene glycol)-poly-l-glutamate complexed with polyethyleneimine−polyglycine for highly efficient gene delivery in vitro and in vivo

Biomaterials Science ◽

10.1039/c8bm00503f ◽

2018 ◽

Vol 6 (11) ◽

pp. 3053-3062 ◽

Cited By ~ 6

Author(s):

Zhaopei Guo ◽

Lin Lin ◽

Jie Chen ◽

Xingzhi Zhou ◽

Hon Fai Chan ◽

...

Keyword(s):

Cancer Therapy ◽

Gene Delivery ◽

Ethylene Glycol ◽

Gene Delivery System ◽

Poly Ethylene Glycol ◽

Highly Efficient ◽

Efficient Gene ◽

Poly Ethylene

The highly efficient gene delivery system with effective serum resistant capacity is promising for cancer therapy.

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A Valid Bisphosphonate Modified Calcium Phosphate-Based Gene Delivery System: Increased Stability and Enhanced Transfection Efficiency In Vitro and In Vivo

Pharmaceutics ◽

10.3390/pharmaceutics11090468 ◽

2019 ◽

Vol 11 (9) ◽

pp. 468 ◽

Cited By ~ 1

Author(s):

Zhao ◽

Li ◽

Chen ◽

Keyword(s):

Calcium Phosphate ◽

Gene Delivery ◽

Tissue Specificity ◽

Transfection Efficiency ◽

Hybrid Nanoparticles ◽

In Vivo Studies ◽

Adsorptive Capacity ◽

Low Cytotoxicity

Calcium phosphate (CaP) nanoparticles, as a promising vehicle for gene delivery, have been widely used owing to their biocompatibility, biodegradability and adsorptive capacity for nucleic acids. Unfortunately, their utility in vivo has been profoundly restricted due to numerous technical barriers such as the lack of tissue specificity and limited transfection efficiency, as well as uncontrollable aggregation over time. To address these issues, an effective conjugate folate-polyethylene glycol-pamidronate (shortened as FA-PEG-Pam) was designed and coated on the surface of CaP/NLS/pDNA (CaP/NDs), forming a versatile gene carrier FA-PEG-Pam/CaP/NDs. Inclusion of FA-PEG-Pam significantly reduced the size of CaP nanoparticles, thus inhibiting the aggregation of CaP nanoparticles. FA-PEG-Pam/CaP/NDs showed better cellular uptake than mPEG-Pam/CaP/NDs, which could be attributed to the high-affinity interactions between FA and highly expressed FR. Meanwhile, FA-PEG-Pam/CaP/NDs had low cytotoxicity and desired effect on inducing apoptosis (71.1%). Furthermore, FA-PEG-Pam/CaP/NDs showed admirable transfection efficiency (63.5%) due to the presence of NLS peptides. What’s more, in vivo studies revealed that the hybrid nanoparticles had supreme antitumor activity (IR% = 58.7%) among the whole preparations. Altogether, FA-PEG-Pam/CaP/NDs was expected to be a hopeful strategy for gene delivery.

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