Bombesin-functionalized superparamagnetic iron oxide nanoparticles for dual-modality MR/NIRFI in mouse models of breast cancer

Abstract

Li Li,1,* Changqiang Wu,2,* Lili Pan,1 Xin Li,1 Anren Kuang,1 Huawei Cai,1 Rong Tian11Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China; 2Sichuan Key Laboratory of Medical Imaging & School of Medical Imaging, North Sichuan Medical College, Nanchong 637000, People’s Republic of ChinaCorrespondence: Huawei CaiDepartment of Nuclear Medicine, West China Hospital, Sichuan University, No. 37, Guoxue Lane, Wuhou District, Chengdu 610041, People’s Republic of ChinaTel [phone]Email [email protected] TianDepartment of Nuclear Medicine, West China Hospital, Sichuan University, No. 37, Guoxue Lane, Wuhou District, Chengdu 610041, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]*These authors contributed equally to this workBackground: The early and accurate detection afforded by imaging techniques significantly reduces mortality in cancer patients. However, it is still a great challenge to achieve satisfactory performance in tumor diagnosis using any single-modality imaging method. Magnetic resonance imaging (MRI) has excellent soft tissue contrast and high spatial resolution, but it suffers from low sensitivity. Fluorescence imaging has high sensitivity, but it is limited by penetration depth. Thus, the combination of the two modes could result in synergistic benefits. Here, we design and characterize a novel dual-modality MR/near-infrared fluorescence imaging (MR/NIRFI) nanomicelle and test its imaging properties in mouse models of breast cancer.Methods: The nanomicelles were prepared by incorporating superparamagnetic iron oxide (SPIO) nanoparticles into 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-5000] micelles to which an NIRF dye and a tumor-targeted peptide (N3-Lys-bombesin, Bom) were conjugated. The nanomicelles were characterized for particle size, zeta potential and morphology. The transverse relaxivity, targeting specificity and imaging ability of the nanomicelles for MR/NIRFI were also examined.Results: The fabricated nanomicelles displayed a well-defined spherical morphology with a mean diameter of 145±56 nm and a high transverse relaxivity (493.9 mM−1·s,−1 3.0T). In MRI, the T2 signal reduction of tumors in the Bom-targeted group was 24.1±5.7% at 4 hrs postinjection, whereas only a 0.1±3.4% (P=0.003) decrease was observed in the nontargeted group. In NIRFI, the contrast increased gradually in the targeted group, and the tumor/muscle ratio increased from 3.7±0.3 at 1 hr to 4.7±0.1 at 2 hrs and to 6.4±0.2 at 4 hrs. No significant changes were observed in the nontargeted group at any time points.Conclusion: Considering all our results, we conclude that these novel MR/NIRFI dual-modality nanomicelles could be promising contrast agents for cancer diagnosis.Keywords: SPIO nanoparticles, magnetic resonance imaging, near-infrared fluorescence imaging, tumor diagnosis

Keywords

• SPIO nanoparticles
• magnetic resonance imaging
• near-infrared fluorescence imaging
• tumor diagnosis