1,721,069 research outputs found
Anticorpo monoclonale isolato o suo frammento legante l'antigene specifico di membrana della prostata, suoi coniugati e suoi usi
No full textAnticorpo monoclonale isolato o suo frammento legante l'antigene specifico di membrana della prostata (Prostate Specific Membrane Aantigen), preferibilmente nella sua forma nativa presente sulla superficie di cellule tumorali. Vengono forniti inoltre un coniugato dell'anticorpo con un principio attivo e forme modificate del frammento anticorpale legante l'antigene. L'anticorpo intero ed il suo frammento riconoscente l'antigene sono utilizzati da soli o coniugati per il trattamento o la diagnosi di tumori o tessuti associati al tumore overesprimenti PSMA, con preferenza per le neoplasie prostatiche
Laser generated gold nanocorals with broadband plasmon absorption for photothermal applications
No full textGold nanoparticles with efficient plasmon absorption in the visible and near infrared (NIR) regions, biocompatibility
and easy surface functionalization are of interest for photothermal applications. Herein we
describe the synthesis and photothermal properties of gold “nanocorals” (AuNC) obtained by laser
irradiation of Au nanospheres (AuNS) dispersed in liquid solution. AuNC are formed in two stages: by
photofragmentation of AuNS, followed by spontaneous unidirectional assembly of gold nanocrystals. The
whole procedure is performed without chemicals or templating compounds, hence the AuNC can be
coated with thiolated molecules in one step. We show that AuNC coated with thiolated polymers are
easily dispersed in an aqueous environment or in organic solvents and can be included in polymeric
matrixes to yield a plasmonic nanocomposite. AuNC dispersions exhibit flat broadband plasmon absorption
ranging from the visible to the NIR and unitary light-to-heat conversion. Besides, in vitro biocompatibility
experiments assessed the absence of cytotoxic effects even at a dose as high as 100 μg mL−1.
These safe-by-designed AuNC are promising for use in various applications such as photothermal cancer
therapy, light-triggered drug release, antimicrobial substrates, optical tomography, obscurant materials
and optical coatings
Immunotoxins and other conjugates: preparation and general characteristics.
No full textTargeted toxins represent an invaluable tool offering a wide range of potential applications, both in experimental models and in the clinics. Here we will review several aspects related to the preparation and properties of carrier molecule-toxin heteroconjugates and fusion toxins
D2B antibody and its scFvD2B fragment in nanomedicine: promising tools in the theranostics of prostate cancer
No full textProstate cancer (PC) is ranked the sixth deadliest cancers among men. If PC is diagnosed at metastasised stages, traditional surgery and radiation therapy have limitations. In the last few decades, antibody therapy has emerged to deliver radioactive drugs to any metastatic PC tumours; thus, improving theranostics results and prolonged patient's survival via effective targeting of prostate specific membrane antigens (PSMA). Full length anti-PSMA antibody, D2B, and its single chain variable fragment, scFvD2B, have been extensively studied as naked or combined with nanoparticles (NPs) in targeted antibody therapy. Such a combination is considered a current hotspot in research as a means to enhance the delivery, binding specificity, and stability of therapeutic or diagnostic agents. In this review, we summarise and compare data from studies published between 1993 & 2021 to highlight the major outputs from in vivo and in vitro applications of D2B and scFvD2B antibodies in PC theranostics. Special focus is set on gold nanoparticles (AuNPs) as a delivery vehicle given their unique physicochemical and biological properties. Our conclusion supports the use of AuNPs-scFvD2B conjugates in future biomedical approaches
Ribosome-inactivating protein-containing conjugates for therapeutic use
No full textA number of plant proteins inhibit protein synthesis by irreversibly inactivating the 60S ribosomal subunit in a catalytical, that is, enzymatic, manner. For this property, they are called ribosome-inactivating proteins (RIPs). Several RIPs are utilized in the preparation of therapeutic heteroconjugates (immunotoxins), obtained either by chemical conjugation of a vehicle molecule to an RIP or by genetic fusion of a targeting molecule and an RIP. In the present review, we will focus on the properties of RIPs and of their immunotoxins. The most recent advancements in this domain will be reported in the following paragraphs
Prostate-specific membrane antigen routing to the cell surface implicates an early association step in the endoplasmic reticulum with lipid microdomains.
No full textHuman Blood biocompatibility and immunogenicity of scFvD2B PEGylated gold nanoparticles
No full text: Single chain variable D2B antibody fragments (scFvD2Bs) exhibit high affinity binding to prostate specific membrane antigens overexpressed in metastatic prostate cancer (PC). Conjugation of scFvD2B to gold nanoparticles (AuNPs) would enhance its stability and plasma half-life circulation to shuttle theranostic agents in PC. In this study, we synthesized PEGylated scFvD2B-AuNPs (AuNPs-scFvD2B-PEG) and tested their integrity, biocompatibility, and immunogenicity in freshly withdrawn human blood. Prior to blood incubation, Zeta potential measurements, UV-Vis spectroscopy, and dynamic light scattering (DLS) were used to assess the physicochemical properties of our nano-complexes in the presence or absence of PEGylation. A surface plasmon resonance band shift of 2 and 4 nm confirmed the successful coating for AuNPs-scFvD2B and AuNPs-scFvD2B-PEG, respectively. Likewise, DLS revealed a size increase of ~3 nm for AuNPs-scFvD2B and ~19 nm for AuNPs-scFvD2B-PEG. Zeta potential increased from -34 mV to -19 mV for AuNPs-scFvD2B and reached -3 mV upon PEGylation. Similar assessment measures were applied post-incubation in human blood with additional immunogenicity tests, such as hemolysis assay, neutrophil function test (NFT), and pyridine formazan extraction. Interestingly, grafting PEG chains on AuNPs-scFvD2B precluded the binding of blood plasma proteins and reduced neutrophil activation level compared with naked AuNPs-citrate counterparts. Most likely, a hydrated negative PEG cloud shielded the NPs rendering blood compatiblility with less than 10% hemolysis. In conclusion, the biocompatible AuNPs-scFvD2B-PEG presents promising characteristics for PC targeted therapy, with minimal protein adsorption affinity, low immunorecognition, and reduced hemolytic activity
Cloning and characterisation of canine prostate-specific membrane antigen
No full textBACKGROUND Prostate-specific membrane antigen (PSMA) is a promising biomarker in the diagnosis of prostate cancer and a potential target for antibody-based therapeutic strategies. We isolated the canine PSMA cDNA and investigated the cellular and biochemical characteristics of the recombinant protein as a potential target for animal preclinical studies of antibody based-therapies. METHODS Canine PSMA cDNA was isolated by PCR, cloned into expression vectors and transfected into COS-1 and MDCK cells. The biosynthesis and glycosylation of the recombinant protein were investigated in pulse-chase experiments, the cellular localization by confocal laser microscopy, the mode of association of PSMA with the membrane with solubilization in different detergents and its quaternary structure in sucrose-density gradients. RESULTS Canine PSMA shows 91% amino acid homology to human PSMA, whereby the major difference is a longer cytoplasmic tail of canine PSMA compared to its human counterpart. Canine PSMA is trafficked efficiently along the secretory pathway, undergoes homodimerization when it acquires complex glycosylated mature form. It associates with detergent-resistant membranes, which act as platforms along its intracellular trafficking. Confocal analysis revealed canine PSMA at the cell surface, Golgi, and the endoplasmic reticulum. A similar distribution is revealed for human PSMA, yet with reduced cell surface levels. CONCLUSIONS The cloning, expression, biosynthesis, processing and localization of canine PSMA in mammalian cells is described. We demonstrate that canine PSMA reveals similar characteristics to human PSMA rendering this protein useful as a translational model for investigations of prostate cancer as well as a suitable antigen for targeted therapy studies in dogs
Prostate-specific membrane antigen associates already in the endoplasmic reticulum with lipid microdomains
No full textPSMA is an integral membrane glycoprotein that is overexpressed in prostate carcinomas rendering this cell surface marker an appropriate target for antibody-vehicled drugs and toxins. We have investigated PSMA biosynthesis, O and N-glycosylation, transport and association with lipid microdomains
- …
