Fluorinated PEG-PEI Coated Magnetic Nanoparticles for siRNA Delivery and CXCR4 Knockdown

Abstract

CXC chemokine receptor 4 (CXCR4) is a promising therapeutic target. Previous studies have shown that intracellular delivery of siRNA to knockdown CXCR4 expression in cancer cells is an effective therapeutic strategy. To prepare efficient magnetic nucleic acid carriers, it is now necessary to improve the endocytosis efficiency of PEGylated magnetic nanoparticles. In our work, Heptafluorobutyryl-polyethylene glycol-polyethyleneimine (FPP) was first prepared and then used to coat magnetic nanoparticles (MNPs) to obtain magnetic nanocarriers FPP@MNPs. The materials were characterized by 19 F-Nuclear Magnetic Resonance (NMR), transmission electron microscope (TEM), energy dispersive spectroscopy (EDS), and dynamic light scattering (DLS). The biosecurity of FPP@MNPs was confirmed by cell viability and apoptosis experiments. Cellular uptake of FPP@MNPs and siRNA transfection enhanced by external magnetic fields were detected by fluorescence microscopy, confocal laser microscopy, and flow cytometry. The results show that the cellular uptake efficiency of FPP@MNPs was significantly improved, and transfection efficiency reached more than 90%. The knockdown of CXCR4 on the 4 T1 cell membrane was confirmed by real-time polymerase chain reaction (RT-PCR) and flow cytometry. In conclusion, the fluorinated cationic polymer-coated magnetic nanoparticles FPP@MNPs can be loaded with siRNA to reduce CXCR4 expression as well as be expected to be efficient universal siRNA carriers.

Multifunctional Mesoporous Silica-Coated Gold Nanorods Mediate Mild Photothermal Heating-Enhanced Gene/Immunotherapy for Colorectal Cancer

“…Considering the results of electrophoretic mobility and the CpG ODNs’ loading efficiency, ASC NPs were prepared at an AS/CpG ODNs weight ratio of 5:1. Coating and modification with positive potential cationic polymers (such as PEG-bPEI) are common means to convert nanoparticles into siRNA carriers [ 48 , 49 ]. Finally, ASCP NPs were prepared by mixing ASC NPs with PEG-bPEI at the weight ratio of 5:1 and by night stirring and centrifugation.…”

Inorganic nanocarriers for siRNA delivery for cancer treatments

“…Moreover, the SPIOs exhibited good MRI contrast effects. In another study, the surface of the SPIOs is modified with heptafluorobutyryl-PEG-PEI molecules and complexed with siRNA specific to CXCR4 (C-X-C chemokine receptor 4) [131]. Usually, CXCR4 is overexpressed in many cancers (especially breast cancers) as it involves in promoting metastasis, forming new tumor blood vessels and developing resistance to chemotherapeutic drugs.…”

Shell‐sheddable and charge switchable magnetic nanoparticle as pH‐sensitive nanocarrier for targeted drug delivery applications

“…PEG has been used as a shell in many nano‐drug delivery systems (NDDSs) to reduce toxic effects and overcome the reticuloendothelial system (RES) in the body 17 . Studies have shown that chemical modification of PEI‐coated IONPs with PEG effectively reduced the positive surface charge of nanoparticles and thus improved the stability and safety of nanoparticles in a physiological environment 18,19 . However, reduction of positive charge through PEGylation inhibit the cellular uptake of nanoparticles at the target site 20 .…”

“…17 Studies have shown that chemical modification of PEI-coated IONPs with PEG effectively reduced the positive surface charge of nanoparticles and thus improved the stability and safety of nanoparticles in a physiological environment. 18,19 However, reduction of positive charge through PEGylation inhibit the cellular uptake of nanoparticles at the target site. 20 To overcome this PEG dilemma, smart shell-sheddable NPs have been developed that could shed their hydrophilic shells in response to environmental stimuli, such as redox [21][22][23][24] and pH 25 at the extracellular compartment of tumor.…”