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Epidermal growth factor receptor (EGFR) targeted nanoparticle are developed by conjugating a single-chain anti-EGFR antibody (ScFvEGFR) to surface functionalized quantum dots (QDs) or magnetic iron oxide (IO) nanoparticles. The results show that ScFvEGFR can be successfully conjugated to the nanoparticles, resulting in compact ScFvEGFR nanoparticles that specifically bind to and are internalized by EGFR-expressing cancer cells, thereby producing a fluorescent signal or magnetic resonance imaging (MRI) contrast. In vivo tumor targeting and uptake of the nanoparticles in human cancer cells is demonstrated after systemic delivery of ScFvEGFR-QDs or ScFvEGFR-IO nanoparticles into an orthotopic pancreatic cancer model. Therefore, ScFvEGFR nanoparticles have potential to be used as a molecular-targeted in vivo tumor imaging agent. Efficient internalization of ScFvEGFR nanoparticles into tumor cells after systemic delivery suggests that the EGFR-targeted nanoparticles can also be used for the targeted delivery of therapeutic agents.

Purpose: Cell-surface receptor-targeted magnetic iron oxide nanoparticles provide molecular magnetic resonance imaging contrast agents for improving specificity of the detection of human cancer. Experimental Design:The present study reports the development of a novel targeted iron oxide nanoparticle using a recombinant peptide containing the amino-terminal fragment of urokinasetype plasminogen activator (uPA) conjugated to magnetic iron oxide nanoparticles amino-terminal fragment conjugated-iron oxide (ATF-IO).This nanoparticle targets uPA receptor, which is overexpressed in breast cancer tissues. Results: ATF-IO nanoparticles are able to specifically bind to and be internalized by uPA receptor^expressing tumor cells. Systemic delivery of ATF-IO nanoparticles into mice bearing s.c. and i.p. mammary tumors leads to the accumulation of the particles in tumors, generating a strong magnetic resonance imaging contrast detectable by a clinical magnetic resonance imaging scanner at a field strength of 3 tesla. Target specificity of ATF-IO nanoparticles showed by in vivo magnetic resonance imaging is further confirmed by near-IR fluorescence imaging of the mammary tumors using near-IR dye-labeled amino-terminal fragment peptides conjugated to iron oxide nanoparticles. Furthermore, mice administered ATF-IO nanoparticles exhibit lower uptake of the particles in the liver and spleen compared with those receiving nontargeted iron oxide nanoparticles. Conclusions: Our results suggest that uPA receptor^targeted ATF-IO nanoparticles have potential as molecularly targeted, dual modality imaging agents for in vivo imaging of breast cancer.Breast cancer is the most common type of cancer and the second leading cause of cancer-related death among women. Novel approaches for the detection of primary and metastatic breast cancers are urgently needed to increase the survival of patients. A promising strategy to improve the specificity and sensitivity of cancer imaging is to use biomarker target -specific imaging probes (1 -3) for image-based diagnosis and treatment monitoring. Currently, targeted radionuclide probes have been used for cancer detection by positron emission tomography or single photon emission tomography (2, 4, 5). Although nuclear imaging modalities show a high sensitivity, they lack good resolution and anatomic localization of the tumor lesion and require complicated and expensive radiochemistry. In addition, the half-life of the radiotracer often limits the ability for dynamic and time-resolved imaging and may not be able to capture the biomarker-targeting agent to reach and accumulate in the tumor. Magnetic resonance imaging offers a high spatial resolution and three-dimensional anatomic details and has been widely used in clinical oncology imaging. Recently, breast magnetic resonance imaging was recommended by the American Cancer Society as a screening approach, adjunct to mammography, for the early detection of breast cancer in women at high risk for this disease (6). Although breast cancer magnetic reson...

A new strategy, dendrimer bridging, is developed for simultaneous formation and functionalization of biocompatible and bioaccessible semiconductor box nanocrystalssa dendron box around each colloidal semiconductor nanocrystal. CdSe plain core or CdSe/ CdS core/shell nanocrystals coated by a monolayer of organic dendron ligands (dendron nanocrystals) with hydroxyl groups as the terminal were chosen as the starting systems because of their potential biocompatibility and proven stability. A generation-two (G2) amineterminated dendrimer was used as the cross-linking and functionalization reagent, which yielded much more stable cross-linked nanocrystals than the simple diamine or trisamine cross-linking reagents did. The chemical, thermal, and photochemical stability of the resulting amine-terminating box nanocrystals (amine box nanocrystals) formed by dendrimer bridging are comparable to that of the first generation box nanocrystals, achieved by ring-closing metathesis (RCM), that are not biocompatible and need to be further functionalized for bioapplications. As expected, the amine groups on the surface of the box nanocrystals provide versatile and reliable conjugation chemistry under mild conditions. Using one of the conjugation methods, biotin molecules were readily coupled onto the amine box nanocrystals. The biomedical applications of those superstable box nanocrystals were demonstrated by the quantitative and reproducible precipitation of the picomole amounts of avidin with the biotinylated box nanocrystals. Experimental results further revealed that the amine box nanocrystals and related derivatives are fully biocompatible to the tested system, have no detectable nonspecific binding, are extremely stable in the desired bioenvironment, and have no noticeable interference with the bioactivities. The exceptional thermal stability further warrants those biocompatible box nanocrystals to be employed in a large temperature range needed for certain applications, such as PCR.

In this study, the conditions and mechanism of antibacterial activity of hydrophilic polymer coated silver nanoparticles (AgNPs) against E. coli O157:H7 (CMCC44828) as model pathogen was studied. The AgNPs were coated with amphiphilic polymer that introduced carboxyl groups on the surface to make it water-soluble. The AgNPs were exposed to various treatment conditions of pH and temperature before these were combined with the E. coli. The mechanism of the antibacterial activity was studied through the formation of reactive oxygen species (ROS) that was later suppressed with antioxidant to establish correlation with the AgNPs antimicrobial activity. Studies were carried out at both anaerobic and aerobic conditions. The results indicated that 5 mg/L AgNPs inhibited ~50% of the growth of 10(6) colony forming units per milliliter (cfu/mL) E. coli cells in liquid Luria-Bertani (LB) medium. This dose-dependent antimicrobial activity was higher at increased temperature (37°C) but was lower when the AgNPs were treated with acid at pH 2 before exposure to the bacteria. It was also established that the conditions of higher antimicrobial effect generated more ROS that was dependent on the presence of oxygen. The antibacterial activity was suppressed in the presence of an antioxidant.