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

Abstract

Purpose Nano dense-silica ( d SiO 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 d SiO 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@ d SiO 2 core–shell nanoparticles were characterized using transmission electron microscopy. Iron content in SPION@ d SiO 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@ d SiO 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@ d SiO 2 –YY146 to target tumor CD146. Results 800ZW–SPION@ d SiO 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@ d SiO 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@ d SiO 2 –YY146 more than the control group 800ZW–SPION@ d SiO 2 . Series of NIRF imaging post intravenous injection of 800ZW–SPION@ d SiO 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 im...

MCAM Mediates Chemoresistance in Small-Cell Lung Cancer via the PI3K/AKT/SOX2 Signaling Pathway

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ImmunoPET for assessing the differential uptake of a CD146-specific monoclonal antibody in lung cancer

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“…PET imaging of YY146 allowed for visualization of small tumor nodules with high specificity in glioblastoma multiforme [14]. To target gastric cancer, superparamagnetic iron oxide nanoparticles (SPIONs) were coated with d SiO 2 , labeled with near-infrared fluorescence (NIRF) dye 800 ZW, and YY146 ( 800 ZW-SPION@ d SiO 2 -YY146) for targeting CD146-expressing gastric cancer [13]. Uptake of 800 ZW-SPION@ d SiO 2 -YY146 was rapid and specific allowing for clear delineation of the tumor at 30 min post-injection with the tumor uptake peaking at 24 h post-injection.…”

Anticancer drug delivery systems based on inorganic nanocarriers with fluorescent tracers

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