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

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.