6 results on '"Hoskins, Clare"'
Search Results
2. Nanomedicine to Overcome Multidrug Resistance Mechanisms in Colon and Pancreatic Cancer: Recent Progress.
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Ortíz, Raúl, Quiñonero, Francisco, García-Pinel, Beatriz, Fuel, Marco, Mesas, Cristina, Cabeza, Laura, Melguizo, Consolación, Prados, Jose, and Hoskins, Clare
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COLON tumors ,PANCREATIC tumors ,PERMEABILITY ,MICRORNA ,GENES ,NANOMEDICINE ,DRUG resistance in cancer cells ,NANOPARTICLES - Abstract
Simple Summary: The cellular mechanisms of drug resistance prevent the correct efficacy of the therapies used in various types of cancer and nanotechnology has been postulated as a possible alternative to avoid them. This review focuses on describing the different mechanisms of drug resistance and dis-covering which nanotechnology-based therapies have been used in recent years to evade them in colon (CRC) and pancreatic cancer (PAC). Here we summarize the use of different types of nanotechnology (mainly nanoparticles) that have shown efficacy in vitro and in vivo in preclinical phases, allowing future in-depth research in CRC and PAC and its translation to future clinical trials. The development of drug resistance is one of the main causes of cancer treatment failure. This phenomenon occurs very frequently in different types of cancer, including colon and pancreatic cancers. However, the underlying molecular mechanisms are not fully understood. In recent years, nanomedicine has improved the delivery and efficacy of drugs, and has decreased their side effects. In addition, it has allowed to design drugs capable of avoiding certain resistance mechanisms of tumors. In this article, we review the main resistance mechanisms in colon and pancreatic cancers, along with the most relevant strategies offered by nanodrugs to overcome this obstacle. These strategies include the inhibition of efflux pumps, the use of specific targets, the development of nanomedicines affecting the environment of cancer-specific tissues, the modulation of DNA repair mechanisms or RNA (miRNA), and specific approaches to damage cancer stem cells, among others. This review aims to illustrate how advanced nanoformulations, including polymeric conjugates, micelles, dendrimers, liposomes, metallic and carbon-based nanoparticles, are allowing to overcome one of the main limitations in the treatment of colon and pancreatic cancers. The future development of nanomedicine opens new horizons for cancer treatment. [ABSTRACT FROM AUTHOR]
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- 2021
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3. Carbon Dots as Promising Tools for Cancer Diagnosis and Therapy.
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Nocito, Giuseppe, Calabrese, Giovanna, Forte, Stefano, Petralia, Salvatore, Puglisi, Caterina, Campolo, Michela, Esposito, Emanuela, Conoci, Sabrina, and Hoskins, Clare
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TUMOR diagnosis ,TUMOR treatment ,THERMOTHERAPY ,CARBON ,PHOTOTHERAPY ,NANOSTRUCTURES ,PHOTOCHEMOTHERAPY - Abstract
Simple Summary: Diagnostic approaches and chemotherapeutic delivery based on nanotechnologies, such as nanoparticles (NPs), could be promising candidates for the new era of cancer research. Recently great attention has been received by carbon-based nanomaterials such as Carbon Dots (CDs), due their variegated physical-chemical properties that makes these systems appealing for multiple use from bioimaging, biosensing, nano-carriers for drug delivery systems to innovative therapeutic agents in photodynamic (PDT) and photothermal therapy (PTT). In this review, we report the last evidence on the application and prospects of CDs as useful nano theranostics tools for cancer diagnosis and therapy. Carbon Dots (CDs) are the latest members of carbon-based nanomaterials, which since their discovery have attracted notable attention due to their chemical and mechanical properties, brilliant fluorescence, high photostability, and good biocompatibility. Together with the ease and affordable preparation costs, these intrinsic features make CDs the most promising nanomaterials for multiple applications in the biological field, such as bioimaging, biotherapy, and gene/drug delivery. This review will illustrate the most recent applications of CDs in the biomedical field, focusing on their biocompatibility, fluorescence, low cytotoxicity, cellular uptake, and theranostic properties to highlight above all their usefulness as a promising tool for cancer diagnosis and therapy. [ABSTRACT FROM AUTHOR]
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- 2021
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4. Doxorubicin-Loaded Gold Nanoarchitectures as a Therapeutic Strategy against Diffuse Intrinsic Pontine Glioma.
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Ung, Caitlin, Tsoli, Maria, Liu, Jie, Cassano, Domenico, Pocoví-Martínez, Salvador, Upton, Dannielle H., Ehteda, Anahid, Mansfeld, Friederike M., Failes, Timothy W., Farfalla, Annafranca, Katsinas, Christopher, Kavallaris, Maria, Arndt, Greg M., Vittorio, Orazio, Cirillo, Giuseppe, Voliani, Valerio, Ziegler, David S., and Hoskins, Clare
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DOXORUBICIN ,WESTERN immunoblotting ,GOLD ,GLIOMAS ,APOPTOSIS ,PASSIFLORA ,SERUM albumin ,CELL proliferation ,NANOPARTICLES - Abstract
Simple Summary: Diffuse intrinsic pontine gliomas (DIPGs) are the most aggressive high-grade gliomas known to affect children. Due to the infiltrative nature of the DIPG tumours in the brainstem, they are very difficult to treat. Unfortunately, children succumb to their disease within 1–2 years from their diagnosis. Novel therapeutic treatments are, thus, urgently needed. Using primary cultures and orthotopic models of DIPG, we evaluated the therapeutic efficacy of passionfruit like nanoarchitectures functionalized with human serum albumin and loaded with doxorubicin (NA-HSA-Dox). We found that NA-HSA-Dox were significantly effective at penetrating DIPG spheroids and subsequently at reducing the proliferation and colony formation in DIPG cells. Although an antitumour effect was not observed in orthotopic models of DIPG, NA-HSA-Dox was well tolerated. These study demonstrates the importance of employing brain tumour orthotopic models for the identification of novel therapies and the need to develop treatments that effectively cross the blood brain barrier. Diffuse Intrinsic Pontine Gliomas (DIPGs) are highly aggressive paediatric brain tumours. Currently, irradiation is the only standard treatment, but is palliative in nature and most patients die within 12 months of diagnosis. Novel therapeutic approaches are urgently needed for the treatment of this devastating disease. We have developed non-persistent gold nano-architectures (NAs) functionalised with human serum albumin (HSA) for the delivery of doxorubicin. Doxorubicin has been previously reported to be cytotoxic in DIPG cells. In this study, we have preclinically evaluated the cytotoxic efficacy of doxorubicin delivered through gold nanoarchitectures (NAs-HSA-Dox). We found that DIPG neurospheres were equally sensitive to doxorubicin and doxorubicin-loaded NAs. Colony formation assays demonstrated greater potency of NAs-HSA-Dox on colony formation compared to doxorubicin. Western blot analysis indicated increased apoptotic markers cleaved Parp, cleaved caspase 3 and phosphorylated H2AX in NAs-HSA-Dox treated DIPG neurospheres. Live cell content and confocal imaging demonstrated significantly higher uptake of NAs-HSA-Dox into DIPG neurospheres compared to doxorubicin alone. Despite the potency of the NAs in vitro, treatment of an orthotopic model of DIPG showed no antitumour effect. This disparate outcome may be due to the integrity of the blood-brain barrier and highlights the need to develop therapies to enhance penetration of drugs into DIPG. [ABSTRACT FROM AUTHOR]
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- 2021
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5. Evaluation of TFR-1 Expression in Feline Mammary Cancer and In Vitro Antitumor Efficacy Study of Doxorubicin-Loaded H-Ferritin Nanocages.
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Rensi, Nicolò, Sammarco, Alessandro, Moccia, Valentina, Calore, Alessandro, Torrigiani, Filippo, Prosperi, Davide, Rizzuto, Maria Antonietta, Bellini, Michela, De Maria, Raffaella, Bonsembiante, Federico, Ferro, Silvia, Zanetti, Rossella, Zappulli, Valentina, Cavicchioli, Laura, and Hoskins, Clare
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DRUG efficacy ,DOXORUBICIN ,FERRITIN ,ANIMAL experimentation ,CELL receptors ,CATS ,METASTASIS ,CELL proliferation ,NANOMEDICINE ,BREAST tumors - Abstract
Simple Summary: Transferrin receptor one (TFR-1), recognized by ferritin, is overexpressed in many tumor cells. This feature has been exploited to produce a selective overload of drugs within tumor cells by creating an engineered ferritin nanocage loaded with doxorubicin (HFn(DOX)). This bionanotechnology has been tested in human cancer, but there are no studies in veterinary oncology. This work, after evaluating the expression of TFR-1 in feline tumors, demonstrated for the first time the effectiveness in vitro of this nanocage in animals. These results confirm that engineered bionanocages also offer unprecedented opportunities for animal cancer to be applied in veterinary medicine and in comparative studies including spontaneous animal models of cancer. The transferrin receptor 1 (TFR-1) has been found overexpressed in a broad range of solid tumors in humans and is, therefore, attracting great interest in clinical oncology for innovative targeted therapies, including nanomedicine. TFR-1 is recognized by H-Ferritin (HFn) and has been exploited to allow selective binding and drug internalization, applying an HFn nanocage loaded with doxorubicin (HFn(DOX)). In veterinary medicine, the role of TFR-1 in animal cancers remains poorly explored, and no attempts to use TFR-1 as a target for drug delivery have been conducted so far. In this study, we determined the TFR-1 expression both in feline mammary carcinomas during tumor progression, as compared to healthy tissue, and, in vitro, in a feline metastatic mammary cancer cell line. The efficacy of HFn(DOX) was compared to treatment with conventional doxorubicin in feline mammary cancer cells. Our results highlighted an increased TFR-1 expression associated with tumor metastatic progression, indicating a more aggressive behavior. Furthermore, it was demonstrated that the use of HFn(DOX) resulted in less proliferation of cells and increased apoptosis when compared to the drug alone. The results of this preliminary study suggest that the use of engineered bionanocages also offers unprecedented opportunities for selective targeted chemotherapy of solid tumors in veterinary medicine. [ABSTRACT FROM AUTHOR]
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- 2021
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6. The Vault Nanoparticle: A Gigantic Ribonucleoprotein Assembly Involved in Diverse Physiological and Pathological Phenomena and an Ideal Nanovector for Drug Delivery and Therapy.
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Frascotti, Gianni, Galbiati, Elisabetta, Mazzucchelli, Matteo, Pozzi, Maria, Salvioni, Lucia, Vertemara, Jacopo, Tortora, Paolo, and Hoskins, Clare
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DRUG delivery systems ,RNA-binding proteins ,CELLULAR signal transduction ,GENE expression ,NANOPARTICLES - Abstract
Simple Summary: In recent decades, a molecular complex referred to as vault nanoparticle has attracted much attention by the scientific community, due to its unique properties. At the molecular scale, it is a huge assembly consisting of 78 97-kDa polypeptide chains enclosing an internal cavity, wherein enzymes involved in DNA integrity maintenance and some small noncoding RNAs are accommodated. Basically, two reasons justify this interest. On the one hand, this complex represents an ideal tool for the targeted delivery of drugs, provided it is suitably engineered, either chemically or genetically; on the other hand, it has been shown to be involved in several cellular pathways and mechanisms that most often result in multidrug resistance. It is therefore expected that a better understanding of the physiological roles of this ribonucleoproteic complex may help develop new therapeutic strategies capable of coping with cancer progression. Here, we provide a comprehensive review of the current knowledge. The vault nanoparticle is a eukaryotic ribonucleoprotein complex consisting of 78 individual 97 kDa-"major vault protein" (MVP) molecules that form two symmetrical, cup-shaped, hollow halves. It has a huge size (72.5 × 41 × 41 nm) and an internal cavity, wherein the vault poly(ADP-ribose) polymerase (vPARP), telomerase-associated protein-1 (TEP1), and some small untranslated RNAs are accommodated. Plenty of literature reports on the biological role(s) of this nanocomplex, as well as its involvement in diseases, mostly oncological ones. Nevertheless, much has still to be understood as to how vault participates in normal and pathological mechanisms. In this comprehensive review, current understanding of its biological roles is discussed. By different mechanisms, vault's individual components are involved in major cellular phenomena, which result in protection against cellular stresses, such as DNA-damaging agents, irradiation, hypoxia, hyperosmotic, and oxidative conditions. These diverse cellular functions are accomplished by different mechanisms, mainly gene expression reprogramming, activation of proliferative/prosurvival signaling pathways, export from the nucleus of DNA-damaging drugs, and import of specific proteins. The cellular functions of this nanocomplex may also result in the onset of pathological conditions, mainly (but not exclusively) tumor proliferation and multidrug resistance. The current understanding of its biological roles in physiological and pathological processes should also provide new hints to extend the scope of its exploitation as a nanocarrier for drug delivery. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
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