Magnetic Nanoparticle Assisted Self-assembly of Cell Penetrating Peptides-Oligonucleotides Complexes for Gene Delivery

Moataz Dowaidar; Hani Nasser Abdelhamid; Mattias Hällbrink; Krista Freimann; Kaido Kurrikoff; Xiaodong Zou; Ülo Langel

doi:10.1038/s41598-017-09803-z

Magnetic Nanoparticle Assisted Self-assembly of Cell Penetrating Peptides-Oligonucleotides Complexes for Gene Delivery

Sci Rep. 2017 Aug 22;7(1):9159. doi: 10.1038/s41598-017-09803-z.

Authors

Moataz Dowaidar¹, Hani Nasser Abdelhamid², Mattias Hällbrink³, Krista Freimann⁴, Kaido Kurrikoff⁴, Xiaodong Zou⁵, Ülo Langel^{6

7}

Affiliations

¹ Department of Neurochemistry, Stockholm University, Svante Arrhenius väg 16B, Stockholm, SE-10691, Sweden. moataz@neurochem.su.se.
² Department of Materials and Environmental Chemistry, Stockholm University, Svante Arrhenius väg 16C, Stockholm, SE-106 91, Sweden.
³ Department of Neurochemistry, Stockholm University, Svante Arrhenius väg 16B, Stockholm, SE-10691, Sweden.
⁴ Laboratory of Molecular Biotechnology, Institute of Technology, University of Tartu, Nooruse, Tartu, 50411, Estonia.
⁵ Department of Materials and Environmental Chemistry, Stockholm University, Svante Arrhenius väg 16C, Stockholm, SE-106 91, Sweden. xzou@mmk.su.se.
⁶ Department of Neurochemistry, Stockholm University, Svante Arrhenius väg 16B, Stockholm, SE-10691, Sweden. ulo@neurochem.su.se.
⁷ Laboratory of Molecular Biotechnology, Institute of Technology, University of Tartu, Nooruse, Tartu, 50411, Estonia. ulo@neurochem.su.se.

Abstract

Magnetic nanoparticles (MNPs, Fe₃O₄) incorporated into the complexes of cell penetrating peptides (CPPs)-oligonucleotides (ONs) promoted the cell transfection for plasmid transfection, splice correction, and gene silencing efficiencies. Six types of cell penetrating peptides (CPPs; PeptFect220 (denoted PF220), PF221, PF222, PF223, PF224 and PF14) and three types of gene therapeutic agents (plasmid (pGL3), splicing correcting oligonucleotides (SCO), and small interfering RNA (siRNA) were investigated. Magnetic nanoparticles incorporated into the complexes of CPPs-pGL3, CPPs-SCO, and CPPs-siRNA showed high cell biocompatibility and efficiently transfected the investigated cells with pGL3, SCO, and siRNA, respectively. Gene transfer vectors formed among PF14, SCO, and MNPs (PF14-SCO-MNPs) showed a superior transfection efficiency (up to 4-fold) compared to the noncovalent PF14-SCO complex, which was previously reported with a higher efficiency compared to commercial vector called Lipofectamine™2000. The high transfection efficiency of the new complexes (CPPs-SCO-MNPs) may be attributed to the morphology, low cytotoxicity, and the synergistic effect of MNPs and CPPs. PF14-pDNA-MNPs is an efficient complex for in vivo gene delivery upon systemic administration. The conjugation of CPPs-ONs with inorganic magnetic nanoparticles (Fe₃O₄) may open new venues for selective and efficient gene therapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line
Cell-Penetrating Peptides / administration & dosage*
Cell-Penetrating Peptides / chemistry
Drug Delivery Systems
Female
Gene Silencing
Gene Transfer Techniques*
HeLa Cells
Humans
Magnetite Nanoparticles / administration & dosage*
Magnetite Nanoparticles / chemistry
Mice
Oligonucleotides / genetics*
Plasmids / genetics
RNA, Small Interfering / genetics
Transfection

Substances

Cell-Penetrating Peptides
Magnetite Nanoparticles
Oligonucleotides
RNA, Small Interfering