Targeting of angiopoietin 2-small interfering RNA plasmid/chitosan magnetic nanoparticles in a mouse model of malignant melanoma in vivo

Abstract

The aim of the present study was to observe the in vivo targeting characteristic of angiopoietin 2-small interfering RNA (Ang2-siRNA) plasmid/chitosan magnetic nanoparticles in an established nude mouse model of malignant melanoma (MM) under an external magnetic field. The nude mouse MM model was first established, then divided into 3 groups, including the control group, the non-targeting group and the target group, the control group was given normal saline and the non-targeting and targeting groups were administrated particles through the tail vein; the non-targeting group was not under external magnetic field and the control group and the targeting group were under external magnetic field for 60 min. The mice were then sacrificed and the tumor tissues were stained with hematoxylin and eosin and Prussian blue in order to verify the particle distributions in the tumor tissues. The control group exhibited negative Prussian blue staining in the tumor tissues, the non-targeting group demonstrated weakly positive Prussian blue staining in tumor tissues and the targeting group revealed strongly positive Prussian blue staining in tumor tissues. Ang2-siRNA plasmid vector/chitosan magnetic nanoparticles directly moved towards tumor tissues under the action of external magnetic field, thus it demonstrated good targeting characteristic.

<p>Effect of Chitosan Magnetic Nanoparticles Loaded with Ang2-siRNA Plasmids on the Growth of Melanoma Xenografts in Nude Mice</p>

“…To address these limitations, chitosan magnetic nanoparticles (CMNPs) containing Ang-2 small interfering RNA (Ang2-siRNA) plasmids were developed, and these nanoparticles could lead to significant inhibition of angiogenesis in a malignant melanoma model. 19 Magnetic iron oxide nanoparticles are the core of Ang2-CMNPs. The Ang2-siRNA plasmid particles were encapsulated by chitosan, which does not increase systemic toxicity and is stable in vivo.…”

“…28 Our previous study also showed that Ang2-CMNPs significantly inhibited the growth of malignant melanoma in vivo. 19 We further evaluated the underlying mechanism of Ang2-CMNP-mediated inhibition of tumor growth. Angiogenesis occurs throughout tumor development and metastasis, and Ang2 has been shown to be essential during the proangiogenic and aggressive phases.…”

“…28 Our previous study also showed that Ang2-CMNPs significantly inhibited the growth of malignant melanoma in vivo. 19 …”

“…The Ang2-siRNA-loaded and chitosan-coated magnetic nanoparticles were preserved by our laboratory and prepared as previously reported; 19 the particle sizes ranged from 55.2 nm to 82.5 nm, with a mean diameter of 67 nm, and the magnetic nanoparticles also exhibited good magnetic responsivity. The pGenesil-3 recombinant plasmid, pGenesil-3 bacterial culture, 1 plus 2 pGenesil-3 Ang2-siRNA recombinant plasmid, and 1 plus 2 pGenesil-3 Ang2-siRNA bacterial culture were all purchased at Wuhan Xima Biotechnology Co., Ltd.…”

“…Recently, chitosan has been shown to be a promising carrier for specific, targeted drug delivery systems to treat cancers and has applications in tissue engineering. 17 , 18 In our previous study, we engineered CMNPs containing Ang-2 small interfering RNA (Ang2-siRNA) plasmids, 19 which are made from a magnetic targeted drug delivery system (MTDDS). 20 The MTDDS, in combination with a stable external magnetic field, allows for the delivery of particles to the chosen target area and retrains the particles at the local site while the medication is released and directly acts on the target site.…”