Alexa Fluor 680-labeled transferrin-cationic (NBD-labeled DOPE-DOTAP) liposome-encapsulated gadopentetate dimeglumine complex

Alexa Fluor 680-labeled transferrin-cationic (NBD-labeled DOPE-DOTAP) liposome-encapsulated gadopentetate dimeglumine complex (Tf^NIR-Lip^NBD-CA complex) is a dual (multimodality) molecular imaging probe with fluorescent and magnetic properties that can be used for imaging tumors with overexpressed transferrin (Tf) receptors (1). Alexa Fluor 680 is a near-infrared (NIR) fluorescence dye with an absorption maximum of 679 nm, an emission maximum of 720 nm, and an extinction coefficient of 180,000 cm−¹M−¹ (2). Gadopentetate dimeglumine (Gd-DTPA) is a water-soluble paramagnetic contrast agent approved by the United States Food and Drug Administration for contrast enhancement in magnetic resonance imaging (MRI) (3).

Tf is part of a family of proteins that includes serum Tf, ovotransferrin, and lactoferrin (4). Serum Tf is a monomeric glycoprotein (molecular mass, 80 kDa) that binds Fe³⁺ for delivery to vertebrate cells through receptor-mediated endocytosis (1). The Tf receptor (TfR) mediates the internalization of iron-loaded Tf into cells (4, 5). The TfR (CD71) is a type II transmembrane glycoprotein and is found primarily as a homodimer (molecular mass, 180 kDa). It also contains other growth regulatory properties in certain normal and malignant cells. The elevated levels of TfR in some malignancies (e.g., 74% breast carcinomas, 76% lung adenocarcinomas, and 93% lung squamous cell carcinomas) and the extracellular accessibility of this molecule make TfR a potential molecular target for Cancer imaging or therapy.

Liposomes (Lips) are small nontoxic vesicles composed of lipid bilayers enclosing aqueous volume, and they are versatile carriers of both therapeutic drugs and imaging agents (5-7). Although Lips are naturally taken up by the reticuloendothelial system, the size, charge, and surface of Lips can be modified for targeting purposes. Because of the intrinsically low sensitivity of MRI and the low penetration of LIGHT, optical and MRI multifunctional probes have been developed as one of the possible approaches to enhance the clinical and research applications of both imaging modalities (1, 8, 9). Shan et al. (1) reported the preparation of a dual probe with fluorescent and magnetic properties based on Lips targeting to TfR-overexpressed tumors. In this Tf^NIR-Lip^NBD-CA complex, Alexa Fluor 680-labeled Tf was linked on the surface of cationic Lips with Gd-DTPA encapsulated inside the vesicles.