Quantum dot loaded immunomicelles for tumor imaging

Abstract

BackgroundOptical imaging is a promising method for the detection of tumors in animals, with speed and minimal invasiveness. We have previously developed a lipid coated quantum dot system that doubles the fluorescence of PEG-grafted quantum dots at half the dose. Here, we describe a tumor-targeted near infrared imaging agent composed of cancer-specific monoclonal anti-nucleosome antibody 2C5, coupled to quantum dot (QD)-containing polymeric micelles, prepared from a polyethylene glycol/phosphatidylethanolamine (PEG-PE) conjugate. Its production is simple and involves no special equipment. Its imaging potential is great since the fluorescence intensity in the tumor is twofold that of non-targeted QD-loaded PEG-PE micelles at one hour after injection.MethodsPara-nitrophenol-containing (5%) PEG-PE quantum dot micelles were produced by the thin layer method. Following hydration, 2C5 antibody was attached to the PEG-PE micelles and the QD-micelles were purified using dialysis. 4T1 breast tumors were inoculated subcutaneously in the flank of the animals. A lung pseudometastatic B16F10 melanoma model was developed using tail vein injection. The contrast agents were injected via the tail vein and mice were depilated, anesthetized and imaged on a Kodak Image Station. Images were taken at one, two, and four hours and analyzed using a methodology that produces normalized signal-to-noise data. This allowed for the comparison between different subjects and time points. For the pseudometastatic model, lungs were removed and imaged ex vivo at one and twenty four hours.ResultsThe contrast agent signal intensity at the tumor was double that of the passively targeted QD-micelles with equally fast and sharply contrasted images. With the side views of the animals only tumor is visible, while in the dorsal view internal organs including liver and kidney are visible. Ex vivo results demonstrated that the agent detects melanoma nodes in a lung pseudometastatic model after a 24 hours wash-out period, while at one hour, only a uniform signal is detected.ConclusionsThe targeted agent produces ultrabright tumor images and double the fluorescence intensity, as rapidly and at the same low dose as the passively targeted agents. It represents a development that may potentially serve to enhance early detection for metastases.

Imaging C-Fos Gene Expression in Burns Using Lipid Coated Spion Nanoparticles

“…Our methodology was to image the gene expression for one day following the administration of the contrast agent in accordance with the protocol established for the gene expression imaging in cerebral tissue and our previous experience with lipid modified contrast agents [7-9, 30,31]. Since we have already established that lipid coated metal nanoparticles accumulate within 2 hours at their target site [19,22,23] and that one day is a sufficient clearance time for non-DNA bond SPIONS, we followed this experimental procedure. Acquisition times were less than 10 min per scan while the retention of contrast agents is published to be several days at their binding site.…”

“…The lipid coating is changing fundamentally the bio-distribution and the site accumulation of the nanoparticles, leading to self-targeting to the desired site within a few hours. It was demonstrated that similar lipid coated nanoparticles accumulate rapidly to the desired sites and clear form the site with equal speed following their peak concentration at one hour [22,23], while they cannot be detected at four hours following their i.v. administration, a much faster biodistribution compared to the conventional, non-lipid coated solid nanoparticles.…”

Immunoconjugates and long circulating systems: Origins, current state of the art and future directions

“…Tumor-targeted quantum dot (QD)-loaded PEG-PE 2C5-immunomicelles that have been developed recently for whole body near infrared imaging (NIR), had a doubled increase in the QD signal intensity and improved detection of metastases in mice [186]. …”

Assessing Breast Cancer Margins Ex Vivo Using Aqueous Quantum-Dot-Molecular Probes

“…By changing particle's size, the emission spectra can be tunable which allows simultaneously imaging of different markers at the same pathological sites [39]. Bioimaging applications of QDs include cell labeling and tracking [40–42], cell proliferation [43], sentinel lymph node mapping [44], brain imaging [45], molecular beacons for DNA detection [46–48], and in vivo tumor detection [49, 50]. For specific target imaging, QDs can be coupled with antibody to detect biomarker on cell's surface.…”