Folate receptor-mediated targeted polymeric gadolinium complexes for magnetic resonance imaging in pulmonary tumor xenografts

Abstract

Abstract. Targeted delivery is a highly desirable strategy for diagnostic imaging due to enhanced efficacy and reduced dosage/toxicity. The need to develop target-specific magnetic resonance imaging (MRI) contrast agents to aid in disease characterization is highly essential. In this study, a specific contrast agent, Gd-DTPA-poly-L-lysine (PL-Gd-DTPA)-folate, was synthesized and evaluated for its efficacy as a targeted agent for the imaging of tumors that overexpress the folate receptor. Folic acid was conjugated to PL-Gd-DTPA via the ε-amino groups. The receptor binding properties of folate-PL-Gd-DTPA were studied in cultured tumor cells that overexpressed the folate receptor. The tumor-selecting properties of folate-PL-Gd-DTPA were then evaluated in BALB/c mice bearing subcutaneously implanted folate receptor-positive tumors. Tissue MR signal intensities were measured at six different time-points. In the in vitro study, the folate-PL-Gd-DTPA was able to bind to these cells, which overexpressed the folate receptor, as with free folic acid. Excellent tumor selectivity was also shown in the animal model; after the success of injection of folate-PL-Gd-DTPA, a maximum intensity increase of 125.4% was observed from pre-injection compared to post-injection images of the tumor at the 48 h time-point. The liver enhancement was non-specific and the muscle signal intensity at any time-point after injection showed no statistical difference with that observed before injection. Folate-PL-Gd-DTPA is a promising, novel receptorspecific MRI contrast agent with potential applications in the imaging of human folate receptor-positive tumors.

Molecular Magnetic Resonance Imaging with Gd(III)-Based Contrast Agents: Challenges and Key Advances

“…Targeted GBCAs have been shown to enter cells through receptor-mediated endocytosis. 21 A caveat of this approach is that the GBCA taken up in this manner can be trapped inside the endosomes. This can severely attenuate the MR signal or even lead to the degradation of GBCAs.…”

Dual-Drug Containing Core-Shell Nanoparticles for Lung Cancer Therapy

“…Furthermore, the MDNPs were surface conjugated with folic acid to actively target the folate receptor-α known to be overexpressed in a number of human cancer cells including lung cancer cells 22 . The glycosylphosphatidylinositol-anchored folate receptor is known to show high affinity for folic acid, which it usually captures to feed the fast-dividing cancer cells 23 – 25 . Therefore, the innovation of this project lies in the development of a novel biodegradable multi-functional nanocarrier that can actively target folate receptor-overexpressing lung cancer cells followed by the release of two different therapeutic agents for non-invasive and effective lung cancer chemo-radiotherapy.…”