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  1. AU="Charalambous, Antonia"
  2. AU="Klikovits, Thomas"
  3. AU="Senyüz, Yakup"
  4. AU="Koth, Laura L"
  5. AU="Qiu, Mingyue"
  6. AU="Hannah Fairbrother"
  7. AU=Parola Philippe
  8. AU="Uervirojnangkoorn, Monarin"
  9. AU="McClellan, Timothy"
  10. AU="William S. J. Horman"
  11. AU="Haque, Munira"
  12. AU="Srinivas Nammi"
  13. AU="Fumika Matsuzaki"
  14. AU="Marchi, Francisco"
  15. AU="Samyra R Cox"
  16. AU="Steffan‐Dewenter, Ingolf"
  17. AU="Mostafa Ahmed Khairy"
  18. AU=Wilkes M S
  19. AU="Zhong, Baichang"
  20. AU="Kirsch, Harald"
  21. AU=Gibson Spencer J

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  1. Artikel ; Online: A synergistic approach for modulating the tumor microenvironment to enhance nano-immunotherapy in sarcomas.

    Mpekris, Fotios / Panagi, Myrofora / Charalambous, Antonia / Voutouri, Chrysovalantis / Michael, Christina / Papoui, Antonia / Stylianopoulos, Triantafyllos

    Neoplasia (New York, N.Y.)

    2024  Band 51, Seite(n) 100990

    Abstract: The lack of properly perfused blood vessels within tumors can significantly hinder the distribution of drugs, leading to reduced treatment effectiveness and having a negative impact on the quality of life of patients with cancer. This problem is ... ...

    Abstract The lack of properly perfused blood vessels within tumors can significantly hinder the distribution of drugs, leading to reduced treatment effectiveness and having a negative impact on the quality of life of patients with cancer. This problem is particularly pronounced in desmoplastic cancers, where interactions between cancer cells, stromal cells, and the fibrotic matrix lead to tumor stiffness and the compression of most blood vessels within the tumor. To address this issue, two mechanotherapy approaches-mechanotherapeutics and ultrasound sonopermeation-have been employed separately to treat vascular abnormalities in tumors and have reached clinical trials. Here, we performed in vivo studies in sarcomas, to explore the conditions under which these two mechanotherapy strategies could be optimally combined to enhance perfusion and the efficacy of nano-immunotherapy. Our findings demonstrate that combination of the anti-histamine drug ketotifen, as a mechanotherapeutic, and sonopermeation effectively alleviates mechanical forces by decreasing 50 % collagen and hyaluronan levels and thus, reshaping the tumor microenvironment. Furthermore, the combined therapy normalizes the tumor vasculature by increasing two-fold the pericytes coverage. This combination not only improves six times tumor perfusion but also enhances drug delivery. As a result, blood vessel functionality is enhanced, leading to increased infiltration by 40 % of immune cells (CD4
    Mesh-Begriff(e) Humans ; CD8-Positive T-Lymphocytes ; Tumor Microenvironment ; Quality of Life ; Immunotherapy ; Sarcoma/drug therapy
    Sprache Englisch
    Erscheinungsdatum 2024-03-22
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1483840-0
    ISSN 1476-5586 ; 1522-8002
    ISSN (online) 1476-5586
    ISSN 1522-8002
    DOI 10.1016/j.neo.2024.100990
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 5203: Hefte anzeigen Standort:
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  2. Artikel ; Online: Pirfenidone-Loaded Polymeric Micelles as an Effective Mechanotherapeutic to Potentiate Immunotherapy in Mouse Tumor Models.

    Mpekris, Fotios / Papaphilippou, Petri Ch / Panagi, Myrofora / Voutouri, Chrysovalantis / Michael, Christina / Charalambous, Antonia / Marinov Dinev, Mariyan / Katsioloudi, Anna / Prokopi-Demetriades, Marianna / Anayiotos, Andreas / Cabral, Horacio / Krasia-Christoforou, Theodora / Stylianopoulos, Triantafyllos

    ACS nano

    2023  Band 17, Heft 24, Seite(n) 24654–24667

    Abstract: Ongoing research is actively exploring the use of immune checkpoint inhibitors to treat solid tumors by inhibiting the PD-1/PD-L1 axis and reactivating the function of cytotoxic T effector cells. Many types of solid tumors, however, are characterized by ... ...

    Abstract Ongoing research is actively exploring the use of immune checkpoint inhibitors to treat solid tumors by inhibiting the PD-1/PD-L1 axis and reactivating the function of cytotoxic T effector cells. Many types of solid tumors, however, are characterized by a dense and stiff stroma and are difficult to treat. Mechanotherapeutics have formed a recent class of drugs that aim to restore biomechanical abnormalities of the tumor microenvironment, related to increased stiffness and hypo-perfusion. Here, we have developed a polymeric formulation containing pirfenidone, which has been successful in restoring the tumor microenvironment in breast tumors and sarcomas. We found that the micellar formulation can induce similar mechanotherapeutic effects to mouse models of 4T1 and E0771 triple negative breast tumors and MCA205 fibrosarcoma tumors but with a dose 100-fold lower than that of the free pirfenidone. Importantly, a combination of pirfenidone-loaded micelles with immune checkpoint inhibition significantly delayed primary tumor growth, leading to a significant improvement in overall survival and in a complete cure for the E0771 tumor model. Furthermore, the combination treatment increased CD4
    Mesh-Begriff(e) Mice ; Animals ; Micelles ; Immunotherapy ; Pyridones/pharmacology ; Pyridones/therapeutic use ; CD8-Positive T-Lymphocytes ; Cell Line, Tumor ; Tumor Microenvironment
    Chemische Substanzen Micelles ; pirfenidone (D7NLD2JX7U) ; Pyridones
    Sprache Englisch
    Erscheinungsdatum 2023-12-06
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ISSN 1936-086X
    ISSN (online) 1936-086X
    DOI 10.1021/acsnano.3c03305
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel: Translating Biomarkers of Cholangiocarcinoma for Theranosis: A Systematic Review.

    Wijetunga, Imeshi / McVeigh, Laura E / Charalambous, Antonia / Antanaviciute, Agne / Carr, Ian M / Nair, Amit / Prasad, K Raj / Ingram, Nicola / Coletta, P Louise

    Cancers

    2020  Band 12, Heft 10

    Abstract: Cholangiocarcinoma (CCA) is a rare disease with poor outcomes and limited research efforts into novel treatment options. A systematic review of CCA biomarkers was undertaken to identify promising biomarkers that may be used for theranosis (therapy and ... ...

    Abstract Cholangiocarcinoma (CCA) is a rare disease with poor outcomes and limited research efforts into novel treatment options. A systematic review of CCA biomarkers was undertaken to identify promising biomarkers that may be used for theranosis (therapy and diagnosis). MEDLINE/EMBASE databases (1996-2019) were systematically searched using two strategies to identify biomarker studies of CCA. The PANTHER Go-Slim classification system and STRING network version 11.0 were used to interrogate the identified biomarkers. The TArget Selection Criteria for Theranosis (TASC-T) score was used to rank identified proteins as potential targetable biomarkers for theranosis. The following proteins scored the highest, CA9, CLDN18, TNC, MMP9, and EGFR, and they were evaluated in detail. None of these biomarkers had high sensitivity or specificity for CCA but have potential for theranosis. This review is unique in that it describes the process of selecting suitable markers for theranosis, which is also applicable to other diseases. This has highlighted existing validated markers of CCA that can be used for active tumor targeting for the future development of targeted theranostic delivery systems. It also emphasizes the relevance of bioinformatics in aiding the search for validated biomarkers that could be repurposed for theranosis.
    Sprache Englisch
    Erscheinungsdatum 2020-09-30
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers12102817
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Freeze-Dried Therapeutic Microbubbles: Stability and Gas Exchange.

    Abou-Saleh, Radwa H / Delaney, Aileen / Ingram, Nicola / Batchelor, Damien V B / Johnson, Benjamin R G / Charalambous, Antonia / Bushby, Richard J / Peyman, Sally A / Coletta, P Louise / Markham, Alexander F / Evans, Stephen D

    ACS applied bio materials

    2020  Band 3, Heft 11, Seite(n) 7840–7848

    Abstract: Microbubbles (MBs) are widely used as contrast enhancement agents for ultrasound imaging and have the potential to enhance therapeutic delivery to diseases such as cancer. Yet, they are only stable in solution for a few hours to days after production, ... ...

    Abstract Microbubbles (MBs) are widely used as contrast enhancement agents for ultrasound imaging and have the potential to enhance therapeutic delivery to diseases such as cancer. Yet, they are only stable in solution for a few hours to days after production, which limits their potential application. Freeze-drying provides long-term storage, ease of transport, and consistency in structure and composition, thereby facilitating their use in clinical settings. Therapeutic microbubbles (thMBs) consisting of MBs with attached therapeutic payload potentially face even greater issues for production, stability, and well-defined drug delivery. The ability to freeze-dry thMBs represents an important step for their translation to the clinic. Here, we show that it is possible to freeze-dry and reconstitute thMBs that consist of lipid-coated MBs with an attached liposomal payload. The thMBs were produced microfluidically, and the liposomes contained either calcein, as a model drug, or gemcitabine. The results show that drug-loaded thMBs can be freeze-dried and stored for at least 6 months. Upon reconstitution, they maintain their structural integrity and drug loading. Furthermore, we show that their
    Sprache Englisch
    Erscheinungsdatum 2020-10-30
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ISSN 2576-6422
    ISSN (online) 2576-6422
    DOI 10.1021/acsabm.0c00982
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Targeted microbubbles carrying lipid-oil-nanodroplets for ultrasound-triggered delivery of the hydrophobic drug, combretastatin A4.

    Charalambous, Antonia / Mico, Victoria / McVeigh, Laura E / Marston, Gemma / Ingram, Nicola / Volpato, Milène / Peyman, Sally A / McLaughlan, James R / Wierzbicki, Antonia / Loadman, Paul M / Bushby, Richard J / Markham, Alexander F / Evans, Stephen D / Coletta, P Louise

    Nanomedicine : nanotechnology, biology, and medicine

    2021  Band 36, Seite(n) 102401

    Abstract: The hydrophobicity of a drug can be a major challenge in its development and prevents the clinical translation of highly potent anti-cancer agents. We have used a lipid-based nanoemulsion termed Lipid-Oil-Nanodroplets (LONDs) for the encapsulation and in ...

    Abstract The hydrophobicity of a drug can be a major challenge in its development and prevents the clinical translation of highly potent anti-cancer agents. We have used a lipid-based nanoemulsion termed Lipid-Oil-Nanodroplets (LONDs) for the encapsulation and in vivo delivery of the poorly bioavailable combretastatin A4 (CA4). Drug delivery with CA4 LONDs was assessed in a xenograft model of colorectal cancer. LC-MS/MS analysis revealed that CA4 LONDs, administered at a drug dose four times lower than drug control, achieved equivalent concentrations of CA4 intratumorally. We then attached CA4 LONDs to microbubbles (MBs) and targeted this construct to VEGFR2. A reduction in tumor perfusion was observed in CA4 LONDs-MBs treated tumors. A combination study with irinotecan demonstrated a greater reduction in tumor growth and perfusion (P = 0.01) compared to irinotecan alone. This study suggests that LONDs, either alone or attached to targeted MBs, have the potential to significantly enhance tumor-specific hydrophobic drug delivery.
    Mesh-Begriff(e) Animals ; Cell Line, Tumor ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/metabolism ; Colorectal Neoplasms/pathology ; Humans ; Hydrophobic and Hydrophilic Interactions ; Lipids/chemistry ; Lipids/pharmacokinetics ; Lipids/pharmacology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Microbubbles ; Nanostructures/chemistry ; Nanostructures/therapeutic use ; Stilbenes/chemistry ; Stilbenes/pharmacokinetics ; Stilbenes/pharmacology ; Ultrasonography ; Xenograft Model Antitumor Assays
    Chemische Substanzen Lipids ; Stilbenes ; fosbretabulin (I5590ES2QZ)
    Sprache Englisch
    Erscheinungsdatum 2021-04-22
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2183417-9
    ISSN 1549-9642 ; 1549-9634
    ISSN (online) 1549-9642
    ISSN 1549-9634
    DOI 10.1016/j.nano.2021.102401
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: Evaluation of lipid-stabilised tripropionin nanodroplets as a delivery route for combretastatin A4.

    Mico, Victoria / Charalambous, Antonia / Peyman, Sally A / Abou-Saleh, Radwa H / Markham, Alexander F / Coletta, P Louise / Evans, Stephen D

    International journal of pharmaceutics

    2017  Band 526, Heft 1-2, Seite(n) 547–555

    Abstract: Lipid-based nanoemulsions are a cheap and elegant route for improving the delivery of hydrophobic drugs. Easy and quick to prepare, nanoemulsions have promise for the delivery of different therapeutic agents. Although multiple studies have investigated ... ...

    Abstract Lipid-based nanoemulsions are a cheap and elegant route for improving the delivery of hydrophobic drugs. Easy and quick to prepare, nanoemulsions have promise for the delivery of different therapeutic agents. Although multiple studies have investigated the effects of the oil and preparation conditions on the size of the nanoemulsion nanodroplets for food applications, analogous studies for nanoemulsions for therapeutic applications are limited. Here we present a study on the production of lipid-stabilised oil nanodroplets (LONDs) towards medical applications. A number of biocompatible oils were used to form LONDs with phospholipid coatings, and among these, squalane and tripropionin were chosen as model oils for subsequent studies. LONDs were formed by high pressure homogenisation, and their size was found to decrease with increasing production pressure. When produced at 175MPa, all LONDs samples exhibited sizes between 100 and 300nm, with polydispersity index PI between 0.1 and 0.3. The LONDs were stable for over six weeks, at 4°C, and also under physiological conditions, showing modest changes in size (<10%). The hydrophobic drug combretastatin A4 (CA4) was encapsulated in tripropionin LONDs with an efficiency of approximately 76%, achieving drug concentration of approximately 1.3mg/ml. SVR mouse endothelial cells treated with CA4 tripropionin LONDs showed the microtubule disruption, characteristic of drug uptake for all tested doses, which suggests successful release of the CA4 from the LONDs.
    Mesh-Begriff(e) Animals ; Cells, Cultured ; Endothelial Cells/drug effects ; Mice ; Nanoparticles/chemistry ; Oils/chemistry ; Stilbenes/administration & dosage ; Triglycerides/chemistry
    Chemische Substanzen Oils ; Stilbenes ; Triglycerides ; tripropionin (F8L8EVQ6QB) ; fosbretabulin (I5590ES2QZ)
    Sprache Englisch
    Erscheinungsdatum 2017-05-08
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article
    ZDB-ID 428962-6
    ISSN 1873-3476 ; 0378-5173
    ISSN (online) 1873-3476
    ISSN 0378-5173
    DOI 10.1016/j.ijpharm.2017.05.009
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Verfügbar in ZB MED Köln/Königswinter

    Zs.A 1409: Hefte anzeigen Standort:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
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  7. Artikel ; Online: Ultrasound-triggered therapeutic microbubbles enhance the efficacy of cytotoxic drugs by increasing circulation and tumor drug accumulation and limiting bioavailability and toxicity in normal tissues.

    Ingram, Nicola / McVeigh, Laura E / Abou-Saleh, Radwa H / Maynard, Juliana / Peyman, Sally A / McLaughlan, James R / Fairclough, Michael / Marston, Gemma / Valleley, Elizabeth M A / Jimenez-Macias, Jorge L / Charalambous, Antonia / Townley, William / Haddrick, Malcolm / Wierzbicki, Antonia / Wright, Alexander / Volpato, Milène / Simpson, Peter B / Treanor, Darren E / Thomson, Neil H /
    Loadman, Paul M / Bushby, Richard J / Johnson, Benjamin R G / Jones, Pamela F / Evans, J Anthony / Freear, Steven / Markham, Alexander F / Evans, Stephen D / Coletta, P Louise

    Theranostics

    2020  Band 10, Heft 24, Seite(n) 10973–10992

    Abstract: Most cancer patients receive chemotherapy at some stage of their treatment which makes improving the efficacy of cytotoxic drugs an ongoing and important goal. Despite large numbers of potent anti-cancer agents being developed, a major obstacle to ... ...

    Abstract Most cancer patients receive chemotherapy at some stage of their treatment which makes improving the efficacy of cytotoxic drugs an ongoing and important goal. Despite large numbers of potent anti-cancer agents being developed, a major obstacle to clinical translation remains the inability to deliver therapeutic doses to a tumor without causing intolerable side effects. To address this problem, there has been intense interest in nanoformulations and targeted delivery to improve cancer outcomes. The aim of this work was to demonstrate how vascular endothelial growth factor receptor 2 (VEGFR2)-targeted, ultrasound-triggered delivery with therapeutic microbubbles (thMBs) could improve the therapeutic range of cytotoxic drugs.
    Mesh-Begriff(e) Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/pharmacokinetics ; Biological Availability ; Cell Line, Tumor ; Colorectal Neoplasms/diagnostic imaging ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/pathology ; Combined Modality Therapy/methods ; Drug Delivery Systems/methods ; Female ; Humans ; Irinotecan ; Microbubbles/therapeutic use ; Microfluidic Analytical Techniques ; Positron-Emission Tomography ; Tissue Distribution/radiation effects ; Ultrasonic Waves ; Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors ; Vascular Endothelial Growth Factor Receptor-2/metabolism ; Xenograft Model Antitumor Assays
    Chemische Substanzen Antineoplastic Agents ; Irinotecan (7673326042) ; KDR protein, human (EC 2.7.10.1) ; Vascular Endothelial Growth Factor Receptor-2 (EC 2.7.10.1)
    Sprache Englisch
    Erscheinungsdatum 2020-09-01
    Erscheinungsland Australia
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2592097-2
    ISSN 1838-7640 ; 1838-7640
    ISSN (online) 1838-7640
    ISSN 1838-7640
    DOI 10.7150/thno.49670
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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