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Review
. 2022 Sep 24;12(19):3323.
doi: 10.3390/nano12193323.

Biocompatible Iron Oxide Nanoparticles for Targeted Cancer Gene Therapy: A Review

Jinsong Zhang  1 , Tianyuan Zhang  1 , Jianqing Gao  1   2
Affiliations
Review

Biocompatible Iron Oxide Nanoparticles for Targeted Cancer Gene Therapy: A Review

Jinsong Zhang et al. Nanomaterials (Basel). .

Abstract

In recent years, gene therapy has made remarkable achievements in tumor treatment. In a successfully cancer gene therapy, a smart gene delivery system is necessary for both protecting the therapeutic genes in circulation and enabling high gene expression in tumor sites. Magnetic iron oxide nanoparticles (IONPs) have demonstrated their bright promise for highly efficient gene delivery target to tumor tissues, partly due to their good biocompatibility, magnetic responsiveness, and extensive functional surface modification. In this review, the latest progress in targeting cancer gene therapy is introduced, and the unique properties of IONPs contributing to the efficient delivery of therapeutic genes are summarized with detailed examples. Furthermore, the diagnosis potentials and synergistic tumor treatment capacity of IONPs are highlighted. In addition, aiming at potential risks during the gene delivery process, several strategies to improve the efficiency or reduce the potential risks of using IONPs for cancer gene therapy are introduced and addressed. The strategies and applications summarized in this review provide a general understanding for the potential applications of IONPs in cancer gene therapy.

Keywords: cancer treatment; gene delivery; iron oxide nanoparticles; tumor diagnosis; tumor targeting.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic illustration of using IONPs to deliver gene drugs to tumor sites.
Figure 2
Figure 2
Gene therapy combining with other strategies to synergistically play a role in the diagnosis and treatment of tumors based on the versatility of IONPs.
Figure 3
Figure 3
IONPs for gene delivery and in vivo tumor imaging. (a) Schematic representation of siPLK1−StAv−SPIONs. (b) In vivo MRI of mice bearing syngeneic orthotopic tumors was performed before and 6 h after intravenous injection of siPLK1−StAv−SPIONs. The dashed line marks the periphery of the tumor. (c) Color contrast images show decreased T2 relaxivity compared to pre−injection. Reprinted with permission from Ref. [86]. Copyright 2016, BMJ Publishing Group Ltd. and British Society of Gastroenterology.
Figure 4
Figure 4
The synergistic effect and immune response elicited by IONP−C/O@LPs. IONPs co−delivered CpG DNA to active immature DCs, synergistically enhancing immune response and antitumor effect. Reprinted with permission from Ref. [97]. Copyright 2022, Wiley−VCH GmbH.
Figure 5
Figure 5
Porous iron oxide nanoparticles (PIONs) loaded with pcDNA3.1−LNC CRYBG3 nanocomplexes (PIONs@pDNA NCs) showed the synergistic ability of MRI, photothermal therapy, and gene therapy to achieve tumor−targeted therapeutics and diagnosis. Reprinted with permission from Ref. [103]. Copyright 2021, Elsevier.
Figure 6
Figure 6
The effect of nanoparticle shape on tumor targeting. (a) Schematic diagram of nanospheres and nanorods. (b) Transvascular transport rates of orthotopic E0771 mammary tumors in mice. Nanorods were transported 4.1 times faster on container walls than nanospheres. (c) Nanoparticle distribution in mouse orthotopic E0771 mammary tumors. Nanorods penetrated 1.7 times the volume of distribution of nanospheres. Reprinted with permission from Ref. [158]. Copyright 2011, Wiley−VCH.
Figure 7
Figure 7
The size and shape of nanoparticles play a crucial role on the hydrodynamic behavior of particles in circulation, including the processes of membrane wrapping and targeting. Reprinted with permission from Ref. [159]. Copyright 2017, American Chemical Society.
Figure 8
Figure 8
DOX−SPBB−siRNA nanocarriers release DOX and siRNA synergistically in A549 lung cancer cells according to the weak acidity of the tumor microenvironment. Reprinted with permission from Ref. [178]. Copyright 2019, American Chemical Society.
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