Bio-functionalized dense-silica nanoparticles for MR/NIRF imaging of CDI46 in gastric cancer

Purpose: Nano dense-silica (dSi[O.sub.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 dSi[O.sub.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@dSi[O.sub.2] core-shell nanoparticles were characterized using transmission electron microscopy. Iron content in SPION@ dSi[O.sub.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@dSi[O.sub.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@dSi[O.sub.2]-YY146 to target tumor CD146. Results: 800ZW-SPION@dSi[O.sub.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 Si[O.sub.2] shell, and the final concentration was 1.7 nmol/mL. Transverse relaxivity of SPION@dSi[O.sub.2] dispersed in water was measured to be 110.57 [mM.sup.-1][s.sup.-1]. Fluorescence activated cell sorter analysis of the nanoparticles in MKN45 cells showed 14-fold binding of 800ZW-SPION@dSi[O.sub.2]-YY146 more than the control group 800ZW-SPION@ dSi[O.sub.2]. Series of NIRF imaging post intravenous injection of 800ZW-SPION@dSi[O.sub.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@dSi[O.sub.2]-YY146 nanoparticles will be applicabl