Magnetic/Upconversion Fluorescent NaGdF₄:Yb,Er Nanoparticle-Based Dual-Modal Molecular Probes for Imaging Tiny Tumors in Vivo

Abstract

Detection of early malignant tumors remains clinically difficult; developing ultrasensitive imaging agents is therefore highly demanded. Owing to the unusual magnetic and optical properties associated with f-electrons, rare-earth elements are very suitable for creating functional materials potentially useful for tumor imaging. Nanometer-sized particles offer such a platform with which versatile unique properties of the rare-earth elements can be integrated. Yet the development of rare-earth nanoparticle-based tumor probes suitable for imaging tiny tumors in vivo remains difficult, which challenges not only the physical properties of the nanoparticles but also the rationality of the probe design. Here we report new approaches for size control synthesis of magnetic/upconversion fluorescent NaGdF4:Yb,Er nanocrystals and their applications for imaging tiny tumors in vivo. By independently varying F(-):Ln(3+) and Na(+):Ln(3+) ratios, the size and shape regulation mechanisms were investigated. By replacing the oleic acid ligand with PEG2000 bearing a maleimide group at one end and two phosphate groups at the other end, PEGylated NaGdF4:Yb,Er nanoparticles with optimized size and upconversion fluorescence were obtained. Accordingly, a dual-modality molecular tumor probe was prepared, as a proof of concept, by covalently attaching antitumor antibody to PEGylated NaGdF4:Yb,Er nanoparticles through a "click" reaction. Systematic investigations on tumor detections, through magnetic resonance imaging and upconversion fluorescence imaging, were carried out to image intraperitoneal tumors and subcutaneous tumors in vivo. Owing to the excellent properties of the molecular probes, tumors smaller than 2 mm was successfully imaged in vivo. In addition, pharmacokinetic studies on differently sized particles were performed to disclose the particle size dependent biodistributions and elimination pathways.

Diagnostic Value of ER, PR, FR and HER-2-Targeted Molecular Probes for Magnetic Resonance Imaging in Patients with Breast Cancer

“…The topical application of molecular probes has several advantages in surgeries, such as the small amounts of required molecular probes and the reduction of systemic toxicity [48]. However, smart molecular probes are required to use MRI in biochemical and clinical research [49]. Our study confirmed that Ab-HER-2-USPIO could specifically bind to BT47 and SKBR3 cells, possibly due to the high expression of HER-2 in these two cell lines [50,51].…”

Ultra-small fluorescent inorganic nanoparticles for bioimaging

“…187,188 Liu et al prepared 5.1 nm NaGdF 4 and 18.5 nm NaGdF 4 :Yb/Er nanoparticles with the same 45 surface modification and investigated their biodistributions in different organs and tissues of mice ( Figure 20). 189 The accumulation of both types of nanoparticles in liver decreased with the circulation time. In contrast, their accumulation in spleen increased with the circulation time.…”

The Application of Up-conversion Nanoparticles Materials in Cancer Diagnosis and Therapy

“…The experimental results show that the RGD peptides is successfully connected to the UCNPs surface, and UCNPs are able to efficiently target the glioma tumor [4]. Later, they will be a wide variety of tumor cells with a high affinity neurotoxin connected to UCNP surface, also realized the targeted UCL imaging.This work shows the UCNP probe in the diagnosis of tumor cells can be used as a molecular target [5][6][7].The Gu group by a new kind of polymer molecules FASOC photosensitizer molecule zinc phthalocyanine (ZnPc) loaded into UCNP surface,and marked with folic acid molecular target tumor, building a set of diagnosis and treatment of nanometer platform integration [8].…”