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

• Published in: International journal of nanomedicine Vol. 10; no. default; pp. 749 - 763
• Main Authors: Wang, Pu, Qu, Yazhuo, Li, Chuan, Yin, Li, Shen, Caifei, Chen, Wei, Yang, Shiming, Bian, Xiuwu, Fang, Dianchun
• Format: Journal Article
• Language: English
• Published: New Zealand Taylor & Francis Ltd 01.01.2015; Dove Press; Dove Medical Press
• Subjects: Angiogenesis; Animals; Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - immunology; Biocompatibility; Biomedical materials; Cancer therapies; CD146 Antigen - immunology; CD146 Antigen - metabolism; Cell Line, Tumor; Drug Delivery Systems; EMT; Esophagus; Female; Fluorescent Antibody Technique; Gastric cancer; Gastroenterology; Humans; Laboratory animals; Life sciences; Magnetic Resonance Imaging - methods; Medical prognosis; Metastasis; Mice; Mice, Nude; Microscopy, Confocal; Microscopy, Fluorescence - methods; Nanoparticles; Nanoparticles - chemistry; Nanotechnology; NMR; Nuclear magnetic resonance; Original Research; Patients; Silicon Dioxide - chemistry; Skin cancer; Spectrometry, Fluorescence - methods; SPION; SPION@dSiO2; Stomach Neoplasms - immunology; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Tumors; xenograft; United States > US; China; nanotechnology; gastric cancer; xenograft; SPION; EMT; SPION@dSiO2
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S62837

Nano dense-silica (dSiO2) 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. Superparamagnetic iron oxide nanoparticles (SPION) were coated with dSiO2 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@dSiO2 core-shell nanoparticles were characterized using transmission electron microscopy. Iron content in SPION@dSiO2 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@dSiO2-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@dSiO2-YY146 to target tumor CD146. 800ZW-SPION@dSiO2-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 SiO2 shell, and the final concentration was 1.7 nmol/mL. Transverse relaxivity of SPION@dSiO2 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@dSiO2-YY146 more than the control group 800ZW-SPION@dSiO2. Series of NIRF imaging post intravenous injection of 800ZW-SPION@dSiO2-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. 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@dSiO2-YY146 nanoparticles will be applicable in tumor for image-guided therapy/surgery.