Bio-functionalized dense-silica nanoparticles for MR/NIRF imaging of CD146 in gastric cancer

Abstract

Purpose

Nano dense-silica ( dSiO ₂) has many advantages such as adjustable core–shell structure, multiple drug delivery, and controllable release behavior. Improving the gastric tumor-specific targeting efficiency based on the development of various strategies is crucial for anti-cancer drug delivery systems.

Methods

Superparamagnetic iron oxide nanoparticles (SPION) were coated with dSiO ₂ as core–shell nanoparticles, and labeled with near infra-red fluorescence (NIRF) dye 800ZW (excitation wavelength: 778 nm/emission wavelength: 806 nm) and anti-CD146 monoclonal antibody YY146 for magnetic resonance (MR)/NIRF imaging study in xenograft gastric cancer model. The morphology and the size of pre- and postlabeling SPION@ dSiO ₂ core–shell nanoparticles were characterized using transmission electron microscopy. Iron content in SPION@ dSiO ₂ nanoparticles was measured by inductively coupled plasma optical emission spectrometry. Fluorescence microscopy and fluorescence-activated cell sorter studies were carried out to confirm the binding specificity of YY146 and 800ZW–SPION@ dSiO ₂–YY146 on MKN45 cells. In vivo and in vitro NIRF imaging, control (nanoparticles only) and blocking studies, and histology were executed on MKN45 tumor-bearing nude mice to estimate the affinity of 800ZW–SPION@ dSiO ₂–YY146 to target tumor CD146.

Results

800ZW–SPION@ dSiO ₂–YY146 nanoparticles were uniformly spherical in shape and dispersed evenly in a cell culture medium. The diameter of the nanoparticle was 20–30 nm with 15 nm SPION core and ~10 nm SiO ₂ shell, and the final concentration was 1.7 nmol/mL. Transverse relaxivity of SPION@ dSiO ₂ dispersed in water was measured to be 110.57 mM ⁻¹·s ⁻¹. Fluorescence activated cell sorter analysis of the nanoparticles in MKN45 cells showed 14-fold binding of 800ZW–SPION@ dSiO ₂–YY146 more than the control group 800ZW–SPION@ dSiO ₂. Series of NIRF imaging post intravenous injection of 800ZW–SPION@ dSiO ₂–YY146 demonstrated that the MKN45 xenograft tumor model could be clearly identified as early as a time point of 30 minutes postinjection. Quantitative analysis revealed that the tumor uptake peaked at 24 hours postinjection.

Conclusion

This is the first successful study of functional nanoparticles for MR/NIRF imaging of cell surface glycoprotein CD146 in gastric cancer model. Our results suggest that 800ZW–SPION@ dSiO ₂–YY146 nanoparticles will be applicable in tumor for image-guided therapy/surgery.