Aza-crown ether locked on polyethyleneimine: solving the contradiction between transfection efficiency and safety during in vivo gene delivery

2020 ◽  
Vol 56 (41) ◽  
pp. 5552-5555
Author(s):  
Shengran Li ◽  
Lin Lin ◽  
Wenliang Wang ◽  
Xinxin Yan ◽  
Binggang Chen ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Crown Ether ◽  
Tumor Targeting ◽  
Transfection Efficiency ◽  
High Gene ◽  
In Vivo Gene Delivery ◽  
Targeting Ability ◽  
Extended Circulation ◽  
Aza Crown Ether

An aza-crown ether derivative to lock a hyperbranched PEI, which endows the PEI with tumor targeting ability, antiserum ability and extended circulation in the blood, meanwhile retaining the high gene complexation and high transfection efficiency.

scholarly journals Semliki Forest virus vectors: efficient vehicles for in vitro and in vivo gene delivery

FEBS Letters ◽  
2001 ◽  
Vol 504 (3) ◽  
pp. 99-103 ◽  
Author(s):  
Kenneth Lundstrom ◽  
Christophe Schweitzer ◽  
Daniel Rotmann ◽  
Danielle Hermann ◽  
Edith M. Schneider ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Semliki Forest Virus ◽  
Virus Vectors ◽  
In Vivo Gene Delivery

scholarly journals In vivo gene delivery by embryonic-stem-cell–derived astrocytes for malignant gliomas

2009 ◽  
Vol 11 (2) ◽  
pp. 102-108 ◽  
Author(s):  
Mahmud Uzzaman ◽  
Gordon Keller ◽  
Isabelle M. Germano
Keyword(s):  
Stem Cell ◽  
Gene Delivery ◽  
Embryonic Stem Cell ◽  
Malignant Gliomas ◽  
Embryonic Stem ◽  
In Vivo Gene Delivery

scholarly journals A Novel TMTP1-modified Theranostic Nanoplatform for Targeted in Vivo NIR-II Fluorescence Imaging-guided Chemotherapy of Cervical Cancer

2021 ◽  
Author(s):  
Alifu Nuernisha ◽  
Rong Ma ◽  
Lijun Zhu ◽  
Zhong Du ◽  
Shuang Chen ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Blood Vessels ◽  
Fluorescence Imaging ◽  
Spatial Resolution ◽  
Self Assembly ◽  
Tumor Targeting ◽  
High Sensitivity ◽  
High Definition ◽  
Targeting Ability

Abstract BackgroundNear-infrared II (NIR-II, 900-1700 nm) fluorescence bioimaging with advantages of good biosafety, excellent spatial resolution, high sensitivity and contrast, has attracted great attentions in biomedical research fields. However, most nanoprobes used for NIR-II fluorescence imaging have poor tumor-targeting ability and therapeutic efficiency. To overcome these limitations, a novel NIR-II-emissive theranostic nanoplatform for imaging and treatment of cervical cancer was designed and prepared. The NIR-II-emissive dye IR-783 and chemotherapy drug doxorubicin (DOX) were encapsulated into liposomes, and the tumor-targeting peptide TMTP1 was conjugated to the surface of the liposomes to form IR-783-DOX-TMTP1 nanoparticles (NPs) via self-assembly methods.ResultsThe IR-783-DOX-TMTP1 NPs showed strong NIR-II emission, excellent biocompatibility, a long lifetime, and low toxicity. Further, high-definition NIR-II fluorescence microscopy images of ear blood vessels and intratumor blood vessels were obtained from IR-783-DOX-TMTP1 NPs-stained mice with high spatial resolution under 808 nm laser excitation. Moreover, IR-783-DOX-TMTP1 NPs showed strong tumor targeting ability and high efficiently chemotherapeutic character towards cervical tumors. ConclusionsThe novel targeting and NIR-II-emissive IR-783-DOX-TMTP1 NPs have potential in diagnosis and therapy for cervical cancer.

scholarly journals FGF Receptor-Mediated Gene Delivery Using Ligands Coupled to PEI-β-CyD

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Yiping Hu ◽  
Guping Tang ◽  
Jun Liu ◽  
Wenxiang Cheng ◽  
Ye Yue ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Gene Delivery ◽  
Human Cancer ◽  
Fibroblast Growth Factor Receptors ◽  
Fgf Receptor ◽  
Human Cancer Cells ◽  
High Gene ◽  
Targeting Ability ◽  
Delivery Efficiency

A novel vector with high gene delivery efficiency and special cell-targeting ability was developed using a good strategy that utilized low-molecular-weight polyethylenimine (PEI; molecular weight: 600 KDa [PEI600]) crosslinked toβ-cyclodextrin (β-CyD) via a facile synthetic route. Fibroblast growth factor receptors (FGFRs) are highly expressed in a variety of human cancer cells and are potential targets for cancer therapy. In this paper, CY11 peptides, which have been proven to combine especially with FGFRs on cell membranes were coupled to PEI-β-CyD usingN-succinimidyl-3-(2-pyridyldithio) propionate as a linker. The ratios of PEI600,β-CyD, and peptide were calculated based on proton integral values obtained from the1H-NMR spectra of the resulting products. Electron microscope observations showed that CY11-PEI-β-CyD can efficiently condense plasmid DNA (pDNA) into nanoparticles of about 200 nm, and MTT assays suggested the decreased toxicity of the polymer. Experiments on gene delivery efficiency in vitro showed that CY11-PEI-β-CyD/pDNA polyplexes had significantly greater transgene activities than PEI-β-CyD/pDNA in the COS-7 and HepG2 cells, which positively expressed FGFR, whereas no such effect was observed in the PC-3 cells, which negatively expressed FGFR. Our current research indicated that the synthesized nonviral vector shows improved gene delivery efficiency and targeting specificity in FGFR-positive cells.

Polyelectrolyte Complexes of Low Molecular Weight PEI and Citric Acid as Efficient and Nontoxic Vectors for in Vitro and in Vivo Gene Delivery

2016 ◽  
Vol 27 (3) ◽  
pp. 549-561 ◽  
Author(s):  
M. Dolores Giron-Gonzalez ◽  
Rafael Salto-Gonzalez ◽  
F. Javier Lopez-Jaramillo ◽  
Alfonso Salinas-Castillo ◽  
Ana Belen Jodar-Reyes ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Citric Acid ◽  
Gene Delivery ◽  
Low Molecular Weight ◽  
Polyelectrolyte Complexes ◽  
In Vivo Gene Delivery

Abstract 39: Adrenal ßArrestin1 Raises Serum Aldosterone Levels And Blood Pressure, Both Significant Stroke Risk Factors, In Experimental Rats And Mice

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Anastasios Lymperopoulos ◽  
Ashley Bathgate ◽  
Norma C Salazar
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Gene Delivery ◽  
Adrenal Cortex ◽  
Stroke Risk ◽  
Fluorescent Protein ◽  
Serum Aldosterone ◽  
Increased Risk ◽  
In Vivo Gene Delivery

Introduction: It is widely accepted nowadays that elevation of serum levels of aldosterone, a mineralocorticoid hormone with toxic effects in several cardiovascular tissues, including the heart and cerebral blood vessels, can significantly raise stroke risk. The success of mineralocorticoid receptor blockers, such as eplerenone, at preventing stroke attacks attests to this. Aldosterone is normally produced and secreted by the adrenal cortex in response to angiotensin II. We recently reported that adrenal βarrestin1 (βarr1) plays a crucial role in the physiological angiotensin II-stimulated aldosterone production in the adrenal cortex, leading to marked elevation of circulating serum aldosterone levels in vivo (Lymperopoulos A. et al., Proc. Natl. Acad. Sci. USA. 2009;106:5825-5830). Hypothesis: Herein, we examined the potential impact of this adrenal βarr1-dependent aldosterone elevation on stroke risk in experimental animals in vivo. Methods: We used the βarr1 knockout (βarr1KO) mouse model, studying it alongside wild type (WT) control mice, and also adult male Sprague-Dawley rats, in which adrenal βarr1 was overexpressed in vivo via adrenal-targeted adenoviral-mediated βarr1 gene transfer. Serum aldosterone was measured by ELISA and blood pressure via telemetry. Results: Serum aldosterone at 7 days post-in vivo gene delivery was markedly elevated in adrenal βarr1-overexpressing rats (536+50 pg/ml), compared to control rats receiving the green fluorescent protein (GFP) adenoviral transgene (235+40 pg/ml, p<0.05, n=5). This translated to a significant increase in mean arterial pressure of the βarr1-overexpressing rats (155+5 mmHg) compared to control GFP-expressing rats (137+8 mmHg, p<0.05, n=5), again at 7 days post-in vivo gene delivery, which was prevented by concurrent eplerenone treatment. In contrast, βarr1KO mice had significantly lower serum aldosterone levels (270+20 pg/ml) compared to WT controls (498+35 pg/ml, p<0.05, n=5), at 4 weeks post-experimental myocardial infarction. Conclusions: Adrenal βarr1 up-regulation can dramatically increase circulating aldosterone levels and systemic blood pressure, thus conferring increased risk for stroke in experimental rodents.

Evaluation of low molecular weight polyethylenimine-introduced chitosan for gene delivery to mesenchymal stem cells

2020 ◽  
Vol 10 (7) ◽  
pp. 1170-1176
Author(s):  
Minchen Liu ◽  
Yulan Hu ◽  
Yi Feng
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Gene Delivery ◽  
Transfection Efficiency ◽  
A549 Cells ◽  
Safety Evaluation ◽  
Physicochemical Characteristics ◽  
Hatching Rate

This study aimed to examine the transfection ability of polyethylenimine (PEI) (1800 Da)-grafted chitosan (10 kDa) (CP), a newly synthesized PEI derivative, in mesenchymal stem cells (MSCs). The safety evaluation of the complex/DNA was studied in vitro and in vivo. In addition, CP/pGL3 was applied to investigate the effects of transfection efficiency. In this study, CP/DNA can be formed with compatible physicochemical characteristics for gene delivery. CP cytotoxicity decreased in A549 cells. Moreover, a zebrafish embryo model was used for evaluating the safety in vivo. Compared to the PEI (25 kDa) group, the zebrafish hatching rate increased and the mortality rate decreased in the CP/DNA group, which provided an indication of the safety of CP. In comparison with chitosan (100 kDa)-PEI (1200 Da), CP's transfection efficiency was higher in both A549 cells and MSCs. This study aimed to lay the foundation for further applications of CP in gene delivery. Therefore, further gene therapy investigations of CP by using MSCs need to be performed.

Alkylimidazolium End-Modified Poly(ethylene glycol) To Form the Mono-ion Complex with Plasmid DNA for in Vivo Gene Delivery

2014 ◽  
Vol 15 (3) ◽  
pp. 997-1001 ◽  
Author(s):  
Shoichiro Asayama ◽  
Atsushi Nohara ◽  
Yoichi Negishi ◽  
Hiroyoshi Kawakami
Keyword(s):  
Gene Delivery ◽  
Ethylene Glycol ◽  
Plasmid Dna ◽  
Poly Ethylene Glycol ◽  
In Vivo Gene Delivery ◽  
Poly Ethylene
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