Search results for "Conjugate"

Loading and release of the complex [Pt(DTBTA)(DMSO)Cl]Cl·CHCl3 with the 2,2′-dithiobis(benzothiazole) ligand into mesoporous silica and studies of an…

2018

Abstract Synthetic delivery systems have great potential for overcoming problems associated with systemic toxicity that accompanies chemotherapy with the use of cisplatin and family of platinum anticancer drugs. Mesoporous silicates have been studied in context of drug delivery and drug targeting. In this paper we report the studies of loading and release of a platinum complex, [Pt(DTBTA)(DMSO)Cl]Cl∙CHCl3 (1) where DTBTA = 2,2′-dithiobis(benzothiazole), that was recently synthesized and structurally characterized. Evaluation in vitro of antitumor activity against a human breast cancer cell line (MCF-7) showed a very potent activity of complex(1). Therefore, we thought to incorporate this co…

Preclinical characterization of IMAB362-vcMMAE, an anti-CLDN18.2 antibody–drug conjugate

2017

A receptor-antibody hybrid hampering MET-driven metastatic spread

2021

AbstractBackgroundThe receptor encoded by the MET oncogene and its ligand Hepatocyte Growth Factor (HGF) are at the core of the invasive-metastatic behavior. In a number of instances genetic alterations result in ligand-independent onset of malignancy (METaddiction). More frequently, ligand stimulation of wild-type MET contributes to progression toward metastasis (METexpedience). Thus, while MET inhibitors alone are effective in the first case, combination therapy with ligand inhibitors is required in the second condition.MethodsIn this paper, we generated hybrid molecules gathering HGF and MET inhibitory properties. This has been achieved by ‘head-to-tail’ or ‘tail-to-head’ fusion of a sin…

Monoclonal Antibodies, Bispecific Antibodies and Antibody-Drug Conjugates in Oncohematology

2020

Background: The therapeutic outcomes and the prognosis of patients with various hematologic malignancies are not always ideal with the current standard of care. Objective: The aim of this study is to analyze the results of the use of monoclonal antibodies, bispecific antibodies and antibody-drug conjugates for the therapy of malignant hemopathies. Methods: A mini-review was achieved using the articles published in Web of Science and PubMed between January 2017 and January 2020 and the new patents were made in this field. Results: Naked monoclonal antibodies have improved the therapeutic results obtained with standard of care, but they also have side effects and the use of some of them can …

Targeted cancer therapy through antibody fragments-decorated nanomedicines.

2017

Active targeting in cancer nanomedicine, for improved delivery of agents and diagnose, has been reviewed as a successful way for facilitating active uptake of theranostic agents by the tumor cells. The application of a targeting moiety in the targeted carrier complexes can play an important role in differentiating between tumor and healthy tissues. The pharmaceutical carriers, as main part of complexes, can be polymeric nanoparticles, micelles, liposomes, nanogels and carbon nanotubes. The antibodies are among the natural ligands with highest affinity and specificity to target pharmaceutical nanoparticle conjugates. However, the limitations, such as size and long circulating half-lives, hin…

Albumin-Folate Conjugates for Drug-targeting in Photodynamic Therapy.

2016

Photodynamic therapy (PDT) is based on the cytotoxicity of photosensitizers in the presence of light. Increased selectivity and effectivity of the treatment is expected if a specific uptake of the photosensitizers into the target cells, often tumor cells, can be achieved. An attractive transporter for that purpose is the folic acid receptor α (FRα), which is overexpressed on the surface of many tumor cells and mediates an endocytotic uptake. Here, we describe the synthesis and photobiological characterization of polar β-carboline derivatives as photosensitizers covalently linked to folate-tagged albumin as the carrier system. The particles were taken up by KB (human carcinoma) cells within …

Synthesis and antiproliferative activity of a natural like glycoconjugate polycyclic compound

2016

Abstract A natural like O -glycoconjugate polycyclic compound 4 was obtained by a multistep procedure starting from N -(3-methyl-1-(4-nitrophenyl)-1 H -pyrazol-5-yl)acetamide. The glycosyl derivative 4 showed antiproliferative activity against all the tumoral cell lines of the NCI panel in the range 0.47–5.43  μ M. Cytofluorimetric analysis performed on MDA-MB231, a very aggressive breast cancer cell line, which does not express estrogen, progesterone and HER-2/neu receptors, showed that 4 is able to induce prolonged cell cycle arrest at G2/M phase and morphological signs of differentiation. These events are correlated with down-regulation of both cyclin B1 and cdc2, the cyclins involved in…

Self-adjuvanting C18 lipid vinil sulfone-PP2A vaccine: study of the induced immunomodulation against Trichuris muris infection

2017

Despite the importance of the adjuvant in the immunization process, very few adjuvants merge with the antigens in vaccines. A synthetic self-adjuvant oleic-vinyl sulfone (OVS) linked to the catalytic region of recombinant serine/threonine phosphatase 2A from the nematode Angiostrongylus costaricensis (rPP2A) was used for intranasal immunization in mice previously infected with Trichuris muris . The animal intranasal immunization with rPP2A-OVS showed a reduction of 99.01% in the number of the nematode eggs and 97.90% in adult. The immunohistochemical analysis of the intestinal sections showed that in immunized animals with lipopeptide the mucus was significantly higher than in the other ex…

Design, synthesis and preliminary evaluation of dopamine-amino acid conjugates as potential D1 dopaminergic modulators.

2016

Abstract The dopamine-amino acid conjugate DA-Phen was firstly designed to obtain a useful prodrug for the therapy of Parkinson's disease, but experimental evidence shows that it effectively interacts with D1 dopamine receptors (D1DRs), leading to an enhancement in cognitive flexibility and to the development of adaptive strategies in aversive mazes, together with a decrease in despair-like behavior. In this paper, homology modelling, molecular dynamics, and site mapping of D1 receptor were carried out with the aim of further performing docking studies on other dopamine conjugates compared with D1 agonists, in the attempt to identify new compounds with potential dopaminergic activity. Two n…

Transient Multivalent Nanobody Targeting to CD206-Expressing Cells via PH-Degradable Nanogels

2020

To target nanomedicines to specific cells, especially of the immune system, nanobodies can be considered as an attractive tool, as they lack the Fc part as compared to traditional antibodies and, thus, prevent unfavorable Fc-receptor mediated mistargeting. For that purpose, we have site-specifically conjugated CD206/MMR-targeting nanobodies to three types of dye-labeled nanogel derivatives: non-degradable nanogels, acid-degradable nanogels (with ketal crosslinks), and single polymer chains (also obtained after nanogel degradation). All of them can be obtained from the same reactive ester precursor block copolymer. After incubation with na&iuml