Chitosan enhances gene delivery of oligonucleotide complexes with magnetic nanoparticles–cell-penetrating peptide

2018 ◽  
Vol 33 (3) ◽  
pp. 392-401 ◽  
Author(s):  
Moataz Dowaidar ◽  
Hani Nasser Abdelhamid ◽  
Mattias Hällbrink ◽  
Ülo Langel ◽  
Xiaodong Zou

Gene-based therapies, including the delivery of oligonucleotides, offer promising methods for the treatment of cancer cells. However, they have various limitations including low efficiency. Herein, cell-penetrating peptides (CPPs)-conjugated chitosan-modified iron oxide magnetic nanoparticles (CPPs-CTS@MNPs) with high biocompatibility as well as high efficiency were tested for the delivery of oligonucleotides such as plasmid pGL3, splice correction oligonucleotides, and small-interfering RNA. A biocompatible nanocomposite, in which CTS@MNPs was incorporated in non-covalent complex with CPPs-oligonucleotide, is developed. Modifying the surface of magnetic nanoparticles with cationic chitosan-modified iron oxide improved the performance of magnetic nanoparticles-CPPs for oligonucleotide delivery. CPPs-CTS@MNPs complexes enhance oligonucleotide transfection compared to CPPs@MNPs or CPPs. The hydrophilic character of CTS@MNPs improves complexation with plasmid pGL3, splice correction oligonucleotides, and small-interfering RNA payload, which consequently resulted in not only strengthening the colloidal stability of the constructed complex but also improving their biocompatibility. Transfection using PF14-splice correction oligonucleotides-CTS@MNPs showed sixfold increase of the transfection compared to splice correction oligonucleotides-PF14 that showed higher transfection than the commercially available lipid-based vector Lipofectamine™ 2000. Nanoscaled CPPs-CTS@MNPs comprise a new family of biomaterials that can circumvent some of the limitations of CPPs or magnetic nanoparticles.

2017 ◽  
Vol 7 ◽  
pp. 1-10 ◽  
Author(s):  
Ly Pärnaste ◽  
Piret Arukuusk ◽  
Kent Langel ◽  
Tanel Tenson ◽  
Ülo Langel

2013 ◽  
Vol 779-780 ◽  
pp. 1674-1677 ◽  
Author(s):  
Dan Lian Huang ◽  
Guang Ming Zeng ◽  
Piao Xu ◽  
Cui Lai ◽  
Mei Hua Zhao ◽  
...  

Immobilized microbe technologies are expected to be effectively used in wastewater treatment. Removal of heavy-metals from wastewater by immobilized Phanerochaete chrysosporium (Pc) with Ca-alginate and iron oxide magnetic nanoparticles (MNPs) was studied. The results showed that a biosorbent as Pc immobilized by Ca-alginate and iron oxide magnetic nanoparticles was successfully developed. And the iron oxide magnetic nanoparticles played an important role in the increase of biosorption capacity of Pc. Energy dispersive spectrometer (EDS) analysis confirmed that metal ions adsorbed to the surface of the biosorbents were partly transmitted to the interior of biosorbents, mainly embedded with iron oxide nanoparticles and Ca-alginate. Moreover, it was found that MNPs-Ca-alginate immobilized Pc showed a good affinity to various heavy metals, such as Pb(II), Zn(II), Cd(II) or Mg(II) and so on. The results proved the high efficiency of the biosorbents for heavy-metal removal and its potential application in the treatment of metal-containing wastewater.


2012 ◽  
Vol 48 (18) ◽  
pp. 2400 ◽  
Author(s):  
Alberto Curcio ◽  
Roberto Marotta ◽  
Andreas Riedinger ◽  
Domenico Palumberi ◽  
Andrea Falqui ◽  
...  

2007 ◽  
Vol 21 (11) ◽  
pp. 2664-2671 ◽  
Author(s):  
Pontus Lundberg ◽  
S. El‐Andaloussi ◽  
T. Sütlü ◽  
H. Johansson ◽  
Ü. Langel

Nanomaterials ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2775
Author(s):  
Anna V. Epanchintseva ◽  
Julia E. Poletaeva ◽  
Ilya S. Dovydenko ◽  
Boris P. Chelobanov ◽  
Dmitrii V. Pyshnyi ◽  
...  

There is an urgent need to develop systems for nucleic acid delivery, especially for the creation of effective therapeutics against various diseases. We have previously shown the feasibility of efficient delivery of small interfering RNA by means of gold nanoparticle-based multilayer nanoconstructs (MLNCs) for suppressing reporter protein synthesis. The present work is aimed at improving the quality of preparations of desired MLNCs, and for this purpose, optimal conditions for their multistep fabrication were found. All steps of this process and MLNC purification were verified using dynamic light scattering, transmission electron microscopy, and UV-Vis spectroscopy. Factors influencing the efficiency of nanocomposite assembly, colloidal stability, and purification quality were identified. These data made it possible to optimize the fabrication of target MLNCs bearing small interfering RNA and to substantially improve end product quality via an increase in its homogeneity and a decrease in the amount of incomplete nanoconstructs. We believe that the proposed approaches and methods will be useful for researchers working with lipid nanoconstructs.


2007 ◽  
Vol 35 (4) ◽  
pp. 770-774 ◽  
Author(s):  
P. Järver ◽  
K. Langel ◽  
S. El-Andaloussi ◽  
Ü. Langel

CPPs (cell-penetrating peptides) can be defined as short peptides that are able to efficiently penetrate cellular lipid bilayers. Because of this remarkable feature, they are excellent candidates regarding alterations in gene expression. CPPs have been utilized in in vivo and in vitro experiments as delivery vectors for different bioactive cargoes. This review focuses on the experiments performed in recent years where CPPs have been used as vectors for multiple effectors of gene expression such as oligonucleotides for antisense, siRNA (small interfering RNA) and decoy dsDNA (double-stranded DNA) applications, and as transfection agents for plasmid delivery.


2007 ◽  
Vol 35 (4) ◽  
pp. 807-810 ◽  
Author(s):  
S.A. Moschos ◽  
A.E. Williams ◽  
M.A. Lindsay

The therapeutic application of siRNA (short interfering RNA) shows promise as an alternative approach to small-molecule inhibitors for the treatment of human disease. However, the major obstacle to its use has been the difficulty in delivering these large anionic molecules in vivo. A potential approach to solving this problem is the chemical conjugation of siRNA to the cationic CPPs (cell-penetrating peptides), Tat-(48–60) (transactivator of transcription) and penetratin, which have been shown previously to mediate protein and peptide delivery in a host of animal models. In this transaction, we review recent studies on the utility of siRNA for the investigation of protein function in the airways/lung. We show that, despite previous studies showing the utility of cationic CPPs in vitro, conjugation of siRNA to Tat-(48–60) and penetratin failed to increase residual siRNA-mediated knockdown of p38 MAPK (mitogen-activated protein kinase) (MAPK14) mRNA in mouse lung in vivo. Significantly, we will also discuss potential non-specific actions and the induction of immunological responses by CPPs and their conjugates and how this might limit their application for siRNA-mediated delivery in vivo.


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