Bifunctional gold nanoparticles for targeted dual imaging of angiotensin converting enzyme

The aim of nanodiagnostics is to identify disease at its earliest stage, particularly at the molecular level. Nanoparticlebased molecular imaging has set a unique platform for cellular tracking, targeted diagnostic studies, and imagemonitored therapy. In the preclinical setting, several modalities, such as fluorescence, positron emission tomography (PET), magnetic resonance imaging (MRI), computed tomography (CT) and ultrasound imaging are used for imaging of the cardiovascular system. Although this conventional imaging describes the extent and severity of cardiovascular diseases such as atherosclerosis or ischemia, molecular imaging is needed to identifying precursors of disease development and progression. Bringing multimodality capability to molecular imaging will harness the complimentary abilities of different techniques, thus optimizing the overall resolution and sensitivity of the resulting scans. The enhanced imaging details will permit more precise diagnosis and control of treatments. In this paper, we present the synthesis and characterization of a dual-imaging contrast agent based on bifunctional gold nanoparticles designed for the targeting of tissue ACE (angiotensin-converting enzyme) and monitoring of cardiovascular diseases. Lisinopril (an ACE inhibitor) was selected as the targeting agent and derivatized with thioctic acid for a stronger anchoring onto gold nanoparticles. A Gd(DOTA) complex was chosen as the MRI tag. The gold core serves as the CT contrast agent. The new nanoprobes prepared not only possess the ability to target tissue ACE but also provided bimodal imaging capabilities (CT and MRI). This bimodal molecular imaging will improve the ability to accurately target diseased tissue at a very early stage, thus diagnosing and then treating patients in the most efficient way.