Tat Peptide Directs Enhanced Clearance and Hepatic Permeability of Magnetic Nanoparticles

Abstract

Superparamagnetic nanoparticles have a number of important biomedical applications, serving as MR contrast agents for imaging specific molecular targets, as reagents for cell labeling and cell tracking, and for the isolation of specific classes of cells. We have determined the physical and biological properties of MION-47 and amino-CLIO, nanoparticles which serve as precursors for the synthesis of targeted MR contrast agents, and Tat-CLIO, a nanoparticle used as a cell labeling reagent. Blood half-lives for MION-47 and amino-CLIO were 682 +/- 34 and 655 +/- 37 min, respectively. The attachment of 9.7 tat peptides per crystal to amino-CLIO resulted in a reduction in blood half-life to 47 +/- 6 min. MION-47, amino-CLIO, and Tat-CLIO were present in highest concentrations in liver and spleen and lymph nodes, where concentrations for all three nanoparticles ranged from 8.80 to 6.11% of injected dose per gram. Twenty-four hours after the intravenous injection of amino-CLIO, the nanoparticle was concentrated in cells surrounding hepatic blood vessels (endothelial and Kupffer cells), in a fashion similar to that obtained with other nanoparticle preparations. In contrast, Tat-CLIO was present as numerous discrete foci of intense fluorescence throughout the parenchyma. Using the peptide as a component of future nanoparticles, it might be possible to design sensors for the detection of macromolecules present in intracellular compartments.

Magnetic Iron Oxide Nanoworms for Tumor Targeting and Imaging

“…3a and Table 1). [17] NWs extracted from the bloodstream after 24 h retained their original shape (Supporting Information Fig. 4) and they showed a slight increase in hydrodynamic size (from ca.…”

“…Dextran-coated magnetic iron oxide (IO) nanoparticles are of particular interest because they show relatively low toxicity and long circulation, and dramatically enhance hydrogen T 2 relaxation in magnetic resonance imaging (MRI). [5,11,[15][16][17][18][19][20] The clinical power of these materials may be amplified by improving MRI relaxivity, blood circulation times, and the homing of such nanoparticles to tumors. Efforts to increase MRI sensitivity have focused on development of new magnetic core materials, [6,12] or on improvements in nanoparticle size [21] or clustering.…”

In vivo cellular imaging of lymphocyte trafficking by MRI: A tumor model approach to cell‐based anticancer therapy

“…Previous studies have reported uptake of dextrancoated nanoparticles ranging from 0.011 to 0.118 pg of iron per cell (usually after 1 hr of incubation) by various tumor cells, and a maximum load of 0.97 pg in primary isolated mouse peritoneal macrophages (19,20). The use of an HIV-1 transactivator (Tat) peptide sequence, for example, can increase their uptake by lymphocytes more than 100-fold compared to untagged nanoparticles (21,22), permitting in vivo tracking of labeled cells (23)(24)(25). Other approaches to increase cellular uptake include receptor-mediated endocytosis, the use of carrier transporters as magnetodendrimers (26,27), and transfection methods combined with simple incubation (28,29).…”

Comparison of lymph node metastases assessment With the use of USPIO‐enhanced MR imaging at 1.5 T versus 3.0 T in a rabbit model

“…Monocrystalline iron oxide nanoparticle (MION)-47 consists of USPIO particles coated with dextran and has a relaxivity R1 of about 21.9 mmol À1 Á sec À1 and a relaxivity R2 of about 44.6 mmol À1 Á sec À1 at 0.47 T, 37 C in water (12). The concentration of iron in USPIO agent is 11.22 mg/mL contained in 20 mmol NaCitrate at pH 8.…”