Root-applied glycinebetaine decreases nitrate accumulation and improves quality in hydroponically grown lettuce.

Leafy vegetables like lettuce (Lactuca sativa L.) naturally have high nitrate content and the European Commission has set maximum level for nitrate in lettuce. Glycinebetaine is an organic osmolyte alleviating plant stress, but its role in leaf nitrate accumulation remains unknown. The uptake of glycinebetaine by lettuce roots, and its potential to regulate lettuce nitrate content and improve plant quality were investigated. Two hydroponic lettuce experiments were conducted with different glycinebetaine application rates (Exp1: 0, 1, 7.5, and 15 mM; Exp2: 0, 1 + 1 + 1, 1 + 10, and 4 mM). Plants were analyzed at varying time points. Root application resulted in glycinebetaine uptake and translocation to the leaves. Glycinebetaine concentrations > 7.5 mM reduced leaf nitrate up to 40% and increased leaf dry matter content. Glycinebetaine showed a positive effect on leaf mineral and amino acid composition. Thus, glycinebetaine could be a novel strategy to reduce the nitrate content in hydroponic lettuce.

Liposomal Tumor Targeting in Drug Delivery Utilizing MMP-2- and MMP-9-Binding Ligands.

Nanotechnology offers an alternative to conventional treatment options by enabling different drug delivery and controlled-release delivery strategies. Liposomes being especially biodegradable and in most cases essentially nontoxic offer a versatile platform for several different delivery approaches that can potentially enhance the delivery and targeting of therapies to tumors. Liposomes penetrate tumors spontaneously as a result of fenestrated blood vessels within tumors, leading to known enhanced permeability and subsequent drug retention effects. In addition, liposomes can be used to carry radioactive moieties, such as radiotracers, which can be bound at multiple locations within liposomes, making them attractive carriers for molecular imaging applications. Phage display is a technique that can deliver various high-affinity and selectivity peptides to different targets. In this study, gelatinase-binding peptides, found by phage display, were attached to liposomes by covalent peptide-PEG-PE anchor creating a targeted drug delivery vehicle. Gelatinases as extracellular targets for tumor targeting offer a viable alternative for tumor targeting. Our findings show that targeted drug delivery is more efficient than non-targeted drug delivery.

Matrix metalloproteinase 9 targeting peptides: syntheses, 68Ga-labeling, and preliminary evaluation in a rat melanoma xenograft model.

Biopanning of tumor cells was used in order to identify matrix metalloproteinase 9 (MMP-9) targeting peptides. The tumor cell targeting peptide (TCTP-1) and two modified versions thereof were evaluated as imaging agents for positron emission tomography (PET) using a rat melanoma xenograft model. For the PET imaging purposes, the 3 peptides were 1,4,7,10-tetraazacyclo-dodecane-N',N'',N''',N''''-tetraacetic acid (DOTA) conjugated and labeled with Gallium-68 ((68)Ga) and preliminarily evaluated: (1) cyclic (68)Ga-DOTA-TCTP-1 with cystine bridge, (2) cyclic (68)Ga-DOTA-lactam-TCTP-1 with a lactam bridge, and (3) linear (68)Ga-DOTA-lin-TCTP-1. The whole-body distribution kinetics and tumor targeting of the intravenously administered (68)Ga-DOTA-peptides were evaluated in vivo by PET and ex vivo by measuring the radioactivity of excised tissues. In addition, the in vivo stability of the radiolabeled peptides in rat plasma, tumor tissue, and urine was studied. All (68)Ga-DOTA-peptides were cleared via the liver and kidneys, and approximately 44% of injected radioactivity was excreted in urine during 120 min after injection. Ex vivo biodistribution studies showed a tumor-to-muscle ratio of 5.5 ± 1.3 (mean ± SD) for (68)Ga-DOTA-TCTP-1, 3.2 ± 0.2 for (68)Ga-DOTA-lactam-TCTP-1, and 3.2 ± 0.6 for (68)Ga-DOTA-lin-TCTP-1 at 120 min after injection. The (68)Ga-DOTA-lactam-TCTP-1 peptide appeared to be the most stable in vivo. The fraction of intact (68)Ga-DOTA-lactam-TCTP-1 in tumor was 59 ± 4.2% at 120 min after injection. The stability was moderate for (68)Ga-DOTA-TCTP-1 and poor for (68)Ga-DOTA-lin-TCTP-1. The possibility of imaging tumors that overexpress MMP-9, such as melanoma, by using radiolabeled TCTP peptides in PET imaging makes these peptides highly attractive for diagnostic and therapeutic applications. However, further modifications to improve the stability and affinity of the peptides are needed.