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  1. Article: Photodynamic Stromal Depletion in Pancreatic Ductal Adenocarcinoma.

    Lintern, Nicole / Smith, Andrew M / Jayne, David G / Khaled, Yazan S

    Cancers

    2023  Volume 15, Issue 16

    Abstract: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest solid malignancies, with a five-year survival of less than 10%. The resistance of the disease and the associated lack of therapeutic response is attributed primarily to its dense, fibrotic ... ...

    Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest solid malignancies, with a five-year survival of less than 10%. The resistance of the disease and the associated lack of therapeutic response is attributed primarily to its dense, fibrotic stroma, which acts as a barrier to drug perfusion and permits tumour survival and invasion. As clinical trials of chemotherapy (CT), radiotherapy (RT), and targeted agents have not been successful, improving the survival rate in unresectable PDAC remains an urgent clinical need. Photodynamic stromal depletion (PSD) is a recent approach that uses visible or near-infrared light to destroy the desmoplastic tissue. Preclinical evidence suggests this can resensitise tumour cells to subsequent therapies whilst averting the tumorigenic effects of tumour-stromal cell interactions. So far, the pre-clinical studies have suggested that PDT can successfully mediate the destruction of various stromal elements without increasing the aggressiveness of the tumour. However, the complexity of this interplay, including the combined tumour promoting and suppressing effects, poses unknowns for the clinical application of photodynamic stromal depletion in PDAC.
    Language English
    Publishing date 2023-08-16
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15164135
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Comparative analysis of whole cell-derived vesicular delivery systems for photodynamic therapy of extrahepatic cholangiocarcinoma.

    Li, Mingjuan / Bosman, Esmeralda D C / Smith, Olivia M / Lintern, Nicole / de Klerk, Daniel J / Sun, Hong / Cheng, Shuqun / Pan, Weiwei / Storm, Gert / Khaled, Yazan S / Heger, Michal

    Journal of photochemistry and photobiology. B, Biology

    2024  Volume 254, Page(s) 112903

    Abstract: This first-in-its-class proof-of-concept study explored the use of bionanovesicles for the delivery of photosensitizer into cultured cholangiocarcinoma cells and subsequent treatment by photodynamic therapy (PDT). Two types of bionanovesicles were ... ...

    Abstract This first-in-its-class proof-of-concept study explored the use of bionanovesicles for the delivery of photosensitizer into cultured cholangiocarcinoma cells and subsequent treatment by photodynamic therapy (PDT). Two types of bionanovesicles were prepared: cellular vesicles (CVs) were fabricated by sonication-mediated nanosizing of cholangiocarcinoma (TFK-1) cells, whereas cell membrane vesicles (CMVs) were produced by TFK-1 cell and organelle membrane isolation and subsequent nanovesicularization by sonication. The bionanovesicles were loaded with zinc phthalocyanine (ZnPC). The CVs and CMVs were characterized (size, polydispersity index, zeta potential, stability, ZnPC encapsulation efficiency, spectral properties) and assayed for tumor (TFK-1) cell association and uptake (flow cytometry, confocal microscopy), intracellular ZnPC distribution (confocal microscopy), dark toxicity (MTS assay), and PDT efficacy (MTS assay). The mean ± SD diameter, polydispersity index, and zeta potential were 134 ± 1 nm, -16.1 ± 0.9, and 0.220 ± 0.013, respectively, for CVs and 172 ± 3 nm, -16.4 ± 1.1, and 0.167 ± 0.022, respectively, for CMVs. Cold storage for 1 wk and incorporation of ZnPC increased bionanovesicular diameter slightly but size remained within the recommended range for in vivo application (136-220 nm). ZnPC was incorporated into CVs and CMVs at an optimal photosensitizer:lipid molar ratio of 0.006 and 0.01, respectively. Both bionanovesicles were avidly taken up by TFK-1 cells, resulting in homogenous intracellular ZnPC dispersion. Photosensitization of TFK-1 cells did not cause dark toxicity, while illumination at 671 nm (35.3 J/cm
    MeSH term(s) Humans ; Photosensitizing Agents/pharmacology ; Photosensitizing Agents/therapeutic use ; Photochemotherapy/methods ; Cholangiocarcinoma/drug therapy ; Bile Duct Neoplasms/drug therapy ; Bile Ducts, Intrahepatic ; Organometallic Compounds/pharmacology ; Zinc Compounds ; Cell Line, Tumor
    Chemical Substances Photosensitizing Agents ; Organometallic Compounds ; Zinc Compounds
    Language English
    Publishing date 2024-04-02
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 623022-2
    ISSN 1873-2682 ; 1011-1344
    ISSN (online) 1873-2682
    ISSN 1011-1344
    DOI 10.1016/j.jphotobiol.2024.112903
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Photoactive imaging and therapy for colorectal cancer using a CEA-Affimer conjugated Foslip nanoparticle.

    Khaled, Yazan S / Khot, M Ibrahim / Aiyappa-Maudsley, Radhika / Maisey, Thomas / Pramanik, Arindam / Tiernan, Jim / Lintern, Nicole / Al-Enezi, Eiman / Shamsuddin, Shazana H / Tomlinson, Darren / Coletta, Louise / Millner, Paul A / Hughes, Thomas A / Jayne, David G

    Nanoscale

    2024  Volume 16, Issue 14, Page(s) 7185–7199

    Abstract: Theranostic nanoparticles hold promise for simultaneous imaging and therapy in colorectal cancer. Carcinoembryonic antigen can be used as a target for these nanoparticles because it is overexpressed in most colorectal cancers. Affimer reagents are ... ...

    Abstract Theranostic nanoparticles hold promise for simultaneous imaging and therapy in colorectal cancer. Carcinoembryonic antigen can be used as a target for these nanoparticles because it is overexpressed in most colorectal cancers. Affimer reagents are synthetic proteins capable of binding specific targets, with additional advantages over antibodies for targeting. We fabricated silica nanoparticles using a water-in-oil microemulsion technique, loaded them with the photosensitiser Foslip, and functionalised the surface with anti-CEA Affimers to facilitate fluorescence imaging and photodynamic therapy of colorectal cancer. CEA-specific fluorescence imaging and phototoxicity were quantified in colorectal cancer cell lines and a LS174T murine xenograft colorectal cancer model. Anti-CEA targeted nanoparticles exhibited CEA-specific fluorescence in the LoVo, LS174T and HCT116 cell lines when compared to control particles (
    MeSH term(s) Humans ; Animals ; Mice ; Carcinoembryonic Antigen ; Colorectal Neoplasms/diagnostic imaging ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/metabolism ; Cell Line, Tumor ; Nanoparticles/therapeutic use ; Mesoporphyrins
    Chemical Substances Carcinoembryonic Antigen ; temoporfin (FU21S769PF) ; Mesoporphyrins
    Language English
    Publishing date 2024-04-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 2515664-0
    ISSN 2040-3372 ; 2040-3364
    ISSN (online) 2040-3372
    ISSN 2040-3364
    DOI 10.1039/d3nr04118b
    Database MEDical Literature Analysis and Retrieval System OnLINE

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