Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Norica Nichita is active.

Publication


Featured researches published by Norica Nichita.


Cancer | 1986

Targeted drug delivery

Stefana M. Petrescu; Gertrude E Costin; Mihaela Trif; Norica Nichita; Raymond A. Dwek

Cancer chemotherapy drugs are neither specific, i.e., they do not act exclusively on the metabolic pathways of cancer cells, nor are they targeted solely toward cancer cells. However, recent research has begun to address, in part, the latter issue. Improved delivery of chemotherapeutic agents to tumor tissue in man appears to be an achievable goal in the next decade. Improved drug delivery includes developing predictive models that allow for laboratory assessment of the best treatment for a patients cancer without exposing the patient to an empirical trial or to the possible morbidity from exposure to a less useful drug, or to the loss of time in the fight against cancer because of ineffectual therapy. Monoclonal antibodies directed against tumor‐associated antigens have the potential to achieve major advances in targeted drug delivery. Monoclonal antibodies may have direct antitumor effects, or they can be used as “homing devices” when attached to a payload and can guide diagnostic or therapeutic agents to the targeted tissues. Carrier systems of all types have become available; these include liposomes and polymeric compounds which can carry drugs, radionuclides, toxins, or other materials in a protected environment. These carriers can also be bound to monoclonal antibodies for possible targeted delivery. Pharmacological sanctuaries have been recognized as a problem in cancer treatment. The best known of these is the central nervous system (CNS). Techniques to temporarily disrupt the blood‐brain barrier are now appearing. Mechanisms to administer therapy directly into the CNS are also being reassessed. Implantable pumps and reservoirs have been used to treat selected organs or for regional perfusions. Other treatments that are regional in scope include administration directly into a cavity or into a tumor. Computerized implantable devices should play a major role in cancer therapy in the future, in pain control as well as antibiotic and hormone administration. In recent years, mathematical models have been developed that can more accurately predict drug distribution and metabolism in various tissues of the body. Such models point the way to more logical designs of chemotherapeutic administration. The expanded use of autologous bone marrow transplantation, along with improving techniques of “purging” the marrow of tumor cells before reinfusion can be anticipated. Pro‐drugs are substances that must be biotransformed in vivo to exert their pharmacologic effect. Certain pro‐drugs that may be more effective or resistance‐avoiding analogues of estab lished chemotherapeutic drugs are currently under development and offer considerable promise. A new era of improved drug delivery is achievable and can lead to greater efficacy of treatment regimens and a higher cure rate while at the same time reducing toxicity. This discussion deals primarily with the currently emerging therapies of monoclonal antibodies, liposomes and intra‐arterial infusions. Cancer 58:573‐583, 1986.The use of pH-sensitive liposomes enhances the delivery of drugs that target the endoplasmic reticulum, reducing the required dosage compared to direct administration of the drug without such liposomes. In particular, antiviral compounds such as N-butyldeoxynojirnmycin can be used in lower amounts when administered in a pH-sensitive liposome.


Journal of Virology | 2010

Hepatitis B Virus Requires Intact Caveolin-1 Function for Productive Infection in HepaRG Cells

Alina Macovei; Cristina Radulescu; Catalin Lazar; Stefana M. Petrescu; David Durantel; Raymond A. Dwek; Nicole Zitzmann; Norica Nichita

ABSTRACT Investigation of the entry pathways of hepatitis B virus (HBV), a member of the family Hepadnaviridae, has been hampered by the lack of versatile in vitro infectivity models. Most concepts of hepadnaviral infection come from the more robust duck HBV system; however, whether the two viruses use the same mechanisms to invade target cells is still a matter of controversy. In this study, we investigate the role of an important plasma membrane component, caveolin-1 (Cav-1), in HBV infection. Caveolins are the main structural components of caveolae, plasma membrane microdomains enriched in cholesterol and sphingolipids, which are involved in the endocytosis of numerous ligands and complex signaling pathways within the cell. We used the HepaRG cell line permissive for HBV infection to stably express dominant-negative Cav-1 and dynamin-2, a GTPase involved in vesicle formation at the plasma membrane and other organelles. The endocytic properties of the newly established cell lines, designated HepaRGCav-1, HepaRGCav-1Δ1-81, HepaRGDyn-2, and HepaRGDyn-2K44A, were validated using specific markers for different entry routes. The cells maintained their properties during cell culture, supported differentiation, and were permissive for HBV infection. The levels of both HBV transcripts and antigens were significantly decreased in cells expressing the mutant proteins, while viral replication was not directly affected. Chemical inhibitors that specifically inhibit clathrin-mediated endocytosis had no effect on HBV infection. We concluded that HBV requires a Cav-1-mediated entry pathway to initiate productive infection in HepaRG cells.


The FASEB Journal | 2010

Uptake and trafficking of liposomes to the endoplasmic reticulum

Stephanie Pollock; Robin Antrobus; Laura Newton; Bettina Kampa; Jan Rossa; Sally Latham; Norica Nichita; Raymond A. Dwek; Nicole Zitzmann

Liposomes are vesicular structures consisting of an aqueous core surrounded by a lipid bilayer. Apart from the cytosol and lysosomes, no other intracellular compartment has been successfully targeted using liposomal delivery. Here, we report the development of liposomes capable of specific targeting to the endoplasmic reticulum (ER) and associated membranes. Using competition and inhibitor assays along with confocal microscopy, we have determined that ER liposomes utilize scavenger and low‐density lipoprotein receptors for endocytosis and enter cells through a caveolin‐ and microtubule‐dependent mechanism. They traffic intact to the ER, where fusion with the ER membrane occurs after 22–25 min, which was confirmed by fluorescence‐dequenching assays. Once inside the ER, tagged lipids intercalate with the ER membrane and are subsequently incorporated into ER‐assembling entities, such as the ER‐budding viruses hepatitis C virus (HCV) and bovine viral diarrhea virus (BVDV), lipid droplets, and secreted lipoproteins. ER liposomes are superior to cytosolic liposome formulations for the intracellular delivery of aqueous cargo, such as HIV‐1 antivirals, and are especially suited for the prolonged delivery of lipids and lipophilic drugs into human cells.—Pollock, S., Antrobus, R, Newton, L., Kampa, B., Rossa, J., Latham, S., Branza Nichita, N., Dwek, R A., Zitzmann, N. Uptake and trafficking of liposomes to the endoplasmic reticulum. FASEB J. 24, 1866–1878 (2010). www.fasebj.org


Proceedings of the National Academy of Sciences of the United States of America | 2010

Polyunsaturated liposomes are antiviral against hepatitis B and C viruses and HIV by decreasing cholesterol levels in infected cells

Stephanie Pollock; Norica Nichita; Annette Böhmer; Cristina Radulescu; Raymond A. Dwek; Nicole Zitzmann

The pressing need for broad-spectrum antivirals could be met by targeting host rather than viral processes. Cholesterol biosynthesis within the infected cell is one promising target for a large number of viral systems, including hepatitis C virus (HCV), hepatitis B virus (HBV) and HIV. Liposomes developed for intracellular, endoplasmic reticulum (ER)-targeted in vivo drug delivery have been modified to include polyunsaturated fatty acids that exert an independent antiviral activity through the reduction of cellular cholesterol. These polyunsaturated ER liposomes (PERLs) have greater activity than lovastatin (Mevacor, Altoprev), which is clinically approved for lowering cholesterol and preventing cardiovascular disease. Treatment of HCV, HBV, and HIV infections with PERLs significantly decreased viral secretion and infectivity, and pretreatment of naïve cells reduced the ability of both HCV and HIV to establish infections because of the decreased levels of plasma membrane cholesterol. Direct competition for cellular receptors was an added effect of PERLs against HCV infections. The greatest antiviral activity in all three systems was the inhibition of viral infectivity through the reduction of virus-associated cholesterol. Our study demonstrates that PERLs are a broadly effective antiviral therapy and should be developed further in combination with encapsulated drug mixtures for enhanced in vivo efficacy.


Biochemical and Biophysical Research Communications | 2002

pH-sensitive liposomes are efficient carriers for endoplasmic reticulum-targeted drugs in mouse melanoma cells

Gertrude-E. Costin; Mihaela Trif; Norica Nichita; Raymond A. Dwek; Stefana M. Petrescu

Tyrosinase, the key enzyme of melanin biosynthesis, is inactivated in melanoma cells following the incubation with the imino-sugar N-butyldeoxynojirimycin, an inhibitor of the endoplasmic reticulum N-glycosylation processing. We have previously shown that tyrosinase inhibition requires high NB-DNJ concentrations, suggesting an inefficient cellular uptake of the drug. Here we show that the use of pH-sensitive liposomes composed of dioleoylphosphatidylethanolamine and cholesteryl hemisuccinate for the delivery of NB-DNJ reduced the required dose for tyrosinase inhibition by a factor of 1000. The results indicate that these pH-sensitive liposomes are efficient carriers for imino-sugars delivery in the endoplasmic reticulum of mammalian cells.


Nano Research | 2015

Self-assemblies of plasmonic gold/layered double hydroxides with highly efficient antiviral effect against the hepatitis B virus

Gabriela Carja; Elena Florentina Grosu; Catalina Petrarean; Norica Nichita

Engineering complex nanocomposites that specifically target the hepatitis B virus (HBV) and overcome the limitations of current therapies such as limited efficacy and serious side effects is very challenging. Here, for the first time, the antiviral effect of engineered plasmonic gold and layered double hydroxide self-assemblies (AuNPs/LDHs) is demonstrated, using HBV as a model virus and hepatoma-derived HepG2.2.215 cells for viral replication, assembly, and secretion of infectious virions and subviral particles. AuNPs/LDHs were obtained by a simple, cost-effective procedure in which small AuNPs (~3.5 nm) were directly obtained and organized on the surface of larger LDH nanoparticles (~150 nm) by exploiting the capability of MgLDH, ZnLDH, and MgFeLDH to manifest their “structural memory” in the aqueous solution of Au(O2CCH3)3. The self-assembly approach of AuNPs and LDHs was assessed by transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), powder X-ray diffraction (PXRD), and UV—Vis analysis (UV–Vis). All AuNPs/LDHs tested reduced the amount of viral and subviral particles released from treated cells by up to 80% and exhibited good cytocompatibility. AuNPs/MgFeLDH showed the highest antiviral HBV response with more than 90% inhibition of HBV secretion for the whole concentration range. Preliminary studies on the mechanism of HBV inhibition reveals that in the presence of AuNPs/LDHs, HBV particles are sequestered within the treated cells. The antiviral and low cytotoxic plasmonic properties of these Au/LDH nanocomposites indicate that they hold significant potential to be tailored as novel efficient therapeutics for the treatment of hepatitis B.


Journal of Basic Microbiology | 2016

Recent advances in human viruses imaging studies

Paula E. Florian; Yves Rouillé; Simona Ruta; Norica Nichita; Anca Roseanu

Microscopy techniques are often exploited by virologists to investigate molecular details of critical steps in viruses’ life cycles such as host cell recognition and entry, genome replication, intracellular trafficking, and release of mature virions. Fluorescence microscopy is the most attractive tool employed to detect intracellular localizations of various stages of the viral infection and monitor the pathogen‐host interactions associated with them. Super‐resolution microscopy techniques have overcome the technical limitations of conventional microscopy and offered new exciting insights into the formation and trafficking of human viruses. In addition, the development of state‐of‐the art electron microscopy techniques has become particularly important in studying virus morphogenesis by revealing ground‐braking ultrastructural details of this process. This review provides recent advances in human viruses imaging in both, in vitro cell culture systems and in vivo, in the animal models recently developed. The newly available imaging technologies bring a major contribution to our understanding of virus pathogenesis and will become an important tool in early diagnosis of viral infection and the development of novel therapeutics to combat the disease.


Biochemistry and Cell Biology | 2012

Endocytosis and trafficking of human lactoferrin in macrophage-like human THP-1 cells (1).

Paula E. Florian; Alina Macovei; Livia E. Sima; Norica Nichita; Inger Mattsby-Baltzer; Anca Roseanu

Different cell types have been reported to internalize lactoferrin (Lf) by specific or nonspecific receptors. Our studies focused on the endocytic pathway of human Lf in macrophage-like THP-1 cells. Lactoferrin was found to be internalized by THP-1 cells differentiated with phorbol myristate acetate. Incubation of cells with chlorpromazine and dansylcadaverine, inhibitors of clathrin-dependent endocytosis, led to a 50% inhibition of Lf internalization compared with untreated cells. Bafilomycin A1 and NH(4)Cl treatment also resulted in 40%-60% inhibition, respectively, suggesting that the internalization of Lf may partly be mediated by acidic endosome-like organelles. Endocytic uptake of Lf was also cholesterol-dependent, as shown by methyl-β-cyclodextrin or nystatin treatment of the cells prior to internalization. Partial colocalization of Lf and EEA-1, a marker specific for early endosomes, could be observed. Colocalization of Lf with a specific endoplasmic reticulum marker was also detected. Our results suggest that Lf is internalized mainly by the clathrin-dependent pathway in THP-1 cells and targets the ER. The physiological consequences of this intracellular trafficking will be the subject of future investigations.


Archive | 2014

Labeling of hepatitis B virus middle envelope protein with enhanced green 1 fluorescent protein

Paula E. Florian; Ramona N. Galantonu; Catalin Lazar; Simona Ruta; Anca Roseanu; Norica Nichita; Sophia Antipolis


Archive | 2002

Ph-sensitive liposomes for targeted drug delivery

Gertrude E Costin; Raymond A. Dwek; Norica Nichita; Stefana M. Petrescu; Mihaela Trif

Collaboration


Dive into the Norica Nichita's collaboration.

Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Researchain Logo
Decentralizing Knowledge