Search results for "targeting"

Targeted tumor imaging of anti-CD20-polymeric nanoparticles developed for the diagnosis of B-cell malignancies

2015

Sara Capolla,1 Chiara Garrovo,2 Sonia Zorzet,1 Andrea Lorenzon,3 Enrico Rampazzo,4 Ruben Spretz,5 Gabriele Pozzato,6 Luis Núñez,7 Claudio Tripodo,8 Paolo Macor,1,9 Stefania Biffi2 1Department of Life Sciences, University of Trieste, 2Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”, Trieste, 3Animal Care Unit, Cluster in Biomedicine (CBM scrl), Trieste, Italy; 4Department of Chemistry “G. Ciamician”, University of Bologna, Bologna, Italy; 5LNK Chemsolutions LLC, Lincoln, NE, USA; 6Department of Medical, Surgery and Health Sciences, University of Trieste, Trieste, Italy; 7Bio-Target, Inc., University of C…

Characterization of Human γδ T Lymphocytes Infiltrating Primary Malignant Melanomas

2012

T lymphocytes are often induced naturally in melanoma patients and infiltrate tumors. Given that gamma delta T cells mediate antigen-specific killing of tumor cells, we studied the representation and the in vitro cytokine production and cytotoxic activity of tumor infiltrating gamma delta T cells from 74 patients with primary melanoma. We found that gamma delta T cells represent the major lymphocyte population infiltrating melanoma, and both V delta 1(+) and V delta 2(+) cells are involved. The majority of melanoma-infiltrating gamma delta cells showed effector memory and terminally-differentiated phenotypes and, accordingly, polyclonal gamma delta T cell lines obtained from tumor-infiltrat…

Conformational control of Bax localization and apoptotic activity by Pro168.

2004

In healthy cells, Bax resides inactive in the cytosol because its COOH-terminal transmembrane region (TMB) is tucked into a hydrophobic pocket. During apoptosis, Bax undergoes a conformational change involving NH2-terminal exposure and translocates to mitochondria to release apoptogenic factors. How this process is regulated remains unknown. We show that the TMB of Bax is both necessary and sufficient for mitochondrial targeting. However, its availability for targeting depends on Pro168 located within the preceding loop region. Pro168 mutants of Bax lack apoptotic activity, cannot rescue the apoptosis-resistant phenotype of Bax/Bak double knockout cells, and are retained in the cytosol even…

Ligand-binding domain determines endoplasmic reticulum exit of AMPA receptors.

2010

AMPA receptors (AMPARs) are tetrameric ion channels that mediate rapid glutamate signaling in neurons and many non-neuronal cell types. Endoplasmic reticulum (ER) quality control mechanisms permit only correctly folded functional receptors to be delivered to the cell surface. We analyzed the biosynthetic maturation and transport of all 12 GluA1–4 subunit splice variants as homomeric receptors and observed robust isoform-dependent differences in ER exit competence and surface expression. In contrast to inefficient ER exit of both GluA3 splice forms and the flop variants of GluA1 and GluA4, prominent plasma membrane expression was observed for the other AMPAR isoforms. Surprisingly, deletion …

Zebrafish Embryos Allow Prediction of Nanoparticle Circulation Times in Mice and Facilitate Quantification of Nanoparticle–Cell Interactions

2020

The zebrafish embryo is a vertebrate well suited for visualizing nanoparticles at high resolution in live animals. Its optical transparency and genetic versatility allow noninvasive, real-time observations of vascular flow of nanoparticles and their interactions with cells throughout the body. As a consequence, this system enables the acquisition of quantitative data that are difficult to obtain in rodents. Until now, a few studies using the zebrafish model have only described semiquantitative results on key nanoparticle parameters. Here, a MACRO dedicated to automated quantitative methods is described for analyzing important parameters of nanoparticle behavior, such as circulation time and…

Lipid nanocarriers containing esters prodrugs of Flurbiprofen. Preparation, physical-chemical characterization and biological studies.

2013

In this paper, the preparation, chemical-physical, technological and in vitro characterization of nanostructured lipid carriers (NLC) carrying R-flurbiprofen ester prodrugs, were analyzed for a potential pharmaceutical application. R-flurbiprofen was chosen as a model drug because it has been found to play an effective role in counteracting secretases involved in neurodegenerative diseases, although it does not cross the Blood Brain Barrier (BBB). In this study, two R-flurbiprofen ester prodrugs (ethyl and hexyl) were successfully synthesized and entrapped into non-pegylated and pegylated NLC. The obtained systems showed average diameters in the colloidal size range, negative zeta potential…

Galactosylated polymeric carriers for liver targeting of sorafenib

2014

In this paper, we describe the preparation of liver-targeted polymeric micelles potentially able to carry sorafenib to hepatocytes for treatment of hepatocarcinoma (HCC), exploiting the presence of carbohydrate receptors, ASGPR. These micelles were prepared starting from a galactosylated polylactide-polyaminoacid conjugate. This latter was obtained by chemical reaction of α,β-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-d,l-aspartamide (PHEA-EDA) with polylactic acid (PLA), and subsequent reaction with lactose, leading to PHEA-EDA-PLA-GAL copolymer. Liver-targeted sorafenib-loaded micelles were obtained in aqueous media at low PHEA-EDA-PLA-GAL copolymer concentration value with nanometer …

Improved radiosynthesis and preliminary in vivo evaluation of the 11C-labeled tetrazine [11C]AE-1 for pretargeted PET imaging

2019

Pretargeted nuclear imaging based on the ligation between tetrazines and nano-sized targeting agents functionalized with trans-cyclooctene (TCO) has recently been shown to improve both imaging contrast and dosimetry in nuclear imaging of nanomedicines. Herein, we describe the improved radiosynthesis of a 11 C-labeled tetrazine ([ 11 C]AE-1) and its preliminary evaluation in both mice and pigs. Pretargeted imaging in mice was carried out using both a new TCO-functionalized polyglutamic acid and a previously reported TCO-functionalized bisphosphonate system as targeting agents. Unfortunately, pretargeted imaging was not successful using these targeting agents in pair with [ 11 C]AE-1. Howeve…

STRATEGIE DI DIREZIONAMENTO ALL’EPATOCARCINOMA DI FARMACI ANTITUMORALI MEDIANTE SISTEMI NANOPARTICELLARI E DI VISUALIZZAZIONE IN CELLULE TUMORALI DEL…

Lo scopo di questo lavoro di tesi è stato quello di realizzare nuovi sistemi nanoparticellari per il direzionamento di farmaci o di agenti per l’imaging, potenzialmente utilizzabili per la terapia e/o per la diagnosi dell’epatocarcinoma (HCC), in particolare per quelle forme caratterizzate dall’overespressione del recettore di membrana degli epatociti ASGP-R o del recettore mitocondriale TSPO. In particolare, nel capitolo 2 sono state descritte la sintesi, la caratterizzazione chimico fisica, la capacità di internalizzazione cellulare e l’efficacia antitumorale di un nuovo sistema nanoparticellare, costituito da un dendrimero a struttura poli-amido-aminica (PAMAM) di quarta generazione, opp…

Multi-Functional Nanogels for Tumor Targeting and Redox-Sensitive Drug and siRNA Delivery

2016

(1) Background: A new family of nanosystems able to discern between normal and tumor cells and to release a therapeutic agent in controlled way were synthetized by e-beam irradiation. This technique permits to obtain biocompatible, sterile, carboxyl-functionalized polyvinylpyrrolidone (PVP-co-acrylic acid) nanogels (NGs); (2) Methods: Here, we performed a targeting strategy based on the recognition of over-expressed proteins on tumor cells, like the folate receptor. The selective targeting was demonstrated by co-culture studies and flow cytometry analysis, using folate conjugated NGs. Moreover, nanoparticles were conjugated to a chemotherapeutic drug or to a pro-apoptotic siRNA through a gl…